The 68 symptoms of the clinical high risk for psychosis: Low similarity among fourteen screening questionnaires.

The Clinical High Risk for psychosis (CHR) is a heterogeneous condition with multiple symptoms. CHR screening is challenging in routine care, as a wide variety of questionnaires exists. We propose to explore the extent to which these questionnaires differ or overlap in item content. We performed a systematic and quantitative analysis of item content in a set of widely-used CHR screening questionnaires. Items were extracted from questionnaires and reworded according to the Structured Interview for Psychosis-Risk Syndromes (SIPS). Then, symptoms were generated from individual items. The Jaccard Index was calculated to assess content overlap. The 14 analysed questionnaires were composed of 347 items, from which 198 symptoms were generated and, in turn, collapsed into 68 distinct symptoms. Positive symptoms were the most commonly represented. The overall overlap across questionnaires showed weak similarity (Jaccard = 0.19±0.50). CHR screening questionnaires might evaluate the same broad clinical construct, but have different scopes within that construct, and may be more or less comprehensive than one another. Clinicians and researchers should be mindful of the specific features of each instrument for optimal CHR screening.

Association between retinal and cortical visual electrophysiological impairments in schizophrenia.

BACKGROUND: Electrophysiological impairments in the magnocellular visual system have been reported among patients with schizophrenia, but previous theories proposed that these deficits may begin in the retina. We therefore sought to evaluate the potential contribution of the retina by comparing retinal and cortical visual electrophysiological impairments between patients with schizophrenia and healthy controls. METHODS: We recruited patients with schizophrenia and age- and sex-matched healthy controls. We recorded the P100 amplitude and latency using electroencephalography (EEG) while projecting low (0.5 cycles/degree) or high (15 cycles/degree) spatial frequency gratings at a temporal frequency of 0 Hz or 8 Hz. We compared the P100 results with previous results for retinal ganglion cell activity (N95) in these participants. We analyzed data using repeated-measures analysis of variance and correlation analyses. RESULTS: We recruited 21 patients with schizophrenia and 29 age- and sex-matched healthy controls. Results showed decreased P100 amplitude and increased P100 latency among patients with schizophrenia compared with healthy controls (p < 0.05). Analyses reported the main effects of spatial and temporal frequency but no interaction effects of spatial or temporal frequency by group. Moreover, correlation analysis indicated a positive association between P100 latency and previous retinal results for N95 latency in the schizophrenia group (p < 0.05). DISCUSSION: Alterations in the P100 wave among patients with schizophrenia are consistent with the deficits in early visual cortical processing shown in the literature. These deficits do not seem to correspond to an isolated magnocellular deficit but appear to be associated with previous retinal measurements. Such an association emphasizes the role of the retina in the occurrence of visual cortical abnormalities in schizophrenia. Studies with coupled electroretinography-EEG measurements are now required to further explore these findings. CLINICAL TRIALS REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02864680.

Visual electrophysiology and neuropsychology in bipolar disorders: A review on current state and perspectives.

Bipolar disorder is a lifelong condition. Today, there is a urgent need to find indicators of the disease. Specifically, they could be useful to improve the diagnosis and the early detection, the prognosis, to estimate the treatment response and to create homogeneous subgroups of patients based on similar pathophysiological mechanisms. Here, we assume that visual electrophysiology in combination with a neuropsychological assessment can give additional data to routine practice, especially to precise specific damages and pathophysiological characteristics of these patients. Visual electrophysiology is characterized by an electroretinogram and the delivery of visual evoked potentials, which measure retinal and visual cortical neuronal functioning in response to visual stimulations. This review highlights the interest of visual electrophysiology and neuropsychology performed in isolation and to present the benefits of combining these measures. We will review the results based on these measures in patients with bipolar disorders. Finally, we argue for the use of innovative techniques such as signal processing and artificial intelligence techniques for routine care and precision medicine in bipolar disorders.

Impaired P100 among regular cannabis users in response to magnocellular biased visual stimuli.

Regular cannabis using causes vision impairment by affecting human retinal neurotransmission. However, studies less considered its impact on the subsequent visual cortical processing, key feature for the integration of the visual signal in brain. We aimed at investigating this purpose in regular cannabis users using spatial frequencies and temporal frequencies filtered visual stimuli. We recruited 45 regular cannabis users and 25 age-matched controls. We recorded visual evoked potentials during the projection of low spatial frequency (0.5 cycles/degree) or high spatial frequency gratings (15 cycles/degree), which were presented statically (0 Hz) or dynamically (8 Hz). We analyzed the amplitude, latency, and area under the curve of both P100 and N170, best EEG markers for early visual processing. Data were compared between groups by repeated measures ANCOVA. Results showed a significant decrease in P100 amplitude among regular cannabis users in low spatial frequency (F(1,67) = 4.43; p = 0.04) and in dynamic condition (F(1,67) = 4.35; p = 0.04). Analysis also reported a decrease in P100 area under the curve in regular cannabis users to low spatial frequency (F(1,67) = 4.31; p = 0.04) and in dynamic condition (F(1,67) = 7.65; p < 0.01). No effect was found on P100 latency, N170 amplitude, latency, or area under the curve. We found alteration of P100 responses to low spatial frequency and dynamic stimuli in regular cannabis users. This result could be interpreted as a preferential magnocellular impairment where such deficit could be linked to glutamatergic dysfunction. As mentioned in the literature, visual and electrophysiological anomalies in schizophrenia are related to a magnocellular dysfunction. Further studies are needed to clarify electrophysiological deficits in both populations. CLINICAL TRIALS REGISTRATION: Electrophysiological Study of the Functioning of Magnocellular Visual Pathway in Regular Cannabis Users (CAUSA MAP). [NCT02864680; ID 2013-A00097-38]. https://clinicaltrials.gov/ct2/show/NCT02864680?cond=Cannabis&cntry=FR&draw=2&rank=1.

Altered central vision and amacrine cells dysfunction as marker of hypodopaminergic activity in treated patients with schizophrenia.

BACKGROUND: Retinal dysfunction is widely documented in schizophrenia using flash (fERG) and pattern electroretinograms (PERG), but the role of dopamine transmission has seldom been explored. METHODS: We explored the role of dopamine transmission by evaluating the spatial location of retinal anomalies using multifocal ERG (mfERG) in photopic condition and the oscillatory potentials (OPs) extracted from fERG measured in scotopic condition in 29 patients with schizophrenia and 29 healthy controls. RESULTS: With the mfERG, our main results revealed reduced amplitudes in the center of the retina: P1 (p < .005) and N2 amplitudes (p < .01) in the <2° region, N1 (p < .0005) and P1 amplitudes (p < .001) in the 2-5° region and P1 amplitude (p < .05) in the 5-10° region. For OPs, our results showed a decrease in the O1 (p < .005), O2 (p < .005), O3 (p < .05) and overall O1, O2, O3 index amplitudes (p < .005) in patients with schizophrenia. CONCLUSIONS: Both the central location of retinal dysfunctions of the mfERG and OPs results could reflect a hypodopaminergic effect in patients with schizophrenia. In future studies, OPs should be considered as a measure to evaluate the hypodopaminergy in patients.

Delayed on- and off-retinal responses of cones pathways in regular cannabis users: An On-Off flash electroretinogram case-control study.

The retina is considered a useful area for investigating synaptic transmission abnormalities in neuropsychiatric disorders, including as a result of using cannabis, the most widely consumed illicit substance in the developed world. The impact of regular cannabis use on retinal function has already been evaluated, using pattern and flash electroretinogram (ERG) to demonstrate a delay in ganglion and bipolar cell response. Using multifocal ERG, it was showed that the delay to be preferentially located in the central retina. ERG tests do not separately examine the impact of cannabis on the On and Off pathways. The purpose of this study is to assess On and Off pathway function using On-Off ERG. We conducted an On-Off ERG test in 42 regular cannabis users and 26 healthy controls. The protocol was compliant with the International Society for Clinical Electrophysiology of Vision (ISCEV) standards. Amplitude and peak time were measured for the a-, b- and d-waves. Results in the regular cannabis users showed a significant increase in the latencies of both the b- and the d-wave (p = 0.020, p = 0.022, respectively, Mann-Whitney U test), with no change in the wave amplitudes. A-wave peak time and amplitude were unchanged. These findings are reflective of an effect of regular cannabis use on the On and Off pathways and are consistent with previous findings which also identified increases in retinal neuron response times. We confirm here that regular cannabis use impacts the post-receptoral cones pathway at the level of bipolar cells, affecting the On and Off pathways.

Retinal ganglion cell dysfunction is correlated with disturbed visual cognition in schizophrenia patients with visual hallucinations.

Patients with schizophrenia have altered visual cognition and retinal functions. No studies have explored if retinal anomalies are related to visual cognition and the presence of visual hallucinations (VH). We explored functional responses of the retinal ganglion cells in schizophrenia patients with or without VH and conducted a neuropsychological evaluation to explore the links between cognition and retinal function. The VH+ group showed poorer visual cognition and we found correlations between the amplitudes of the P50 and the N95 waves and visual cognition. Our results provide arguments for a link between retinal dysfunction, impaired visual processing and VH in schizophrenia.

Retinal dysfunctions in a patient with a clinical high risk for psychosis and severe visual disturbances: A single case report.

AIM: Psychosis can be preceded by a clinical high risk for psychosis (CHR) and visual anomalies are predictors of transition to psychosis. Visual retinal processing is altered in psychosis, but no study has explored the links between visual symptoms and retinal functions in CHR patients. We report here the case of NR, an antipsychotic-naive young adult with CHR and severe visual symptoms in whom we explored the retinal function. METHODS: A flash electroretinogram (fERG) and a pattern electroretinogram (pERG) protocol were conducted and we compared NR results to a group of patients with schizophrenia and a group of healthy controls. RESULTS: Despites an overlap between the measures of NR and the two groups, visual analyses revealed that NR showed increased b-wave implicit time (rod response) compared to the control group and NR's response was at an intermediate level between two subgroups of schizophrenia patients regarding presence or absence of visual hallucinations. DISCUSSION: The relevance of retinal dysfunctions as a marker of vulnerability for psychosis is discussed.

Retinal ganglion cells dysfunctions in schizophrenia patients with or without visual hallucinations.

The electroretinogram has revealed photoreceptor, bipolar cell, and, in one prior study, retinal ganglion cell (RGC) dysfunction in schizophrenia. The structural abnormalities of the RGC are well documented in schizophrenia and such abnormalities have been associated with visual hallucinations (VH) in neurological disorders. The goals of this study were: 1) to examine the functional responses of photoreceptors and RGC in schizophrenia patients in comparison with healthy controls; and 2) to compare the extent of retinal dysfunction in schizophrenia patients with or without VH. We recorded the flash electroretinogram in scotopic and photopic conditions, and the pattern electroretinogram, in schizophrenia patients (n = 29) and healthy controls (n = 29). Schizophrenia patients were divided in two groups: schizophrenia patients with VH (VH group, n = 12) and schizophrenia patients with auditory hallucinations or no hallucinations (AHNH group, n = 17). Our results replicate previous findings regarding photoreceptor dysfunction in schizophrenia. PERG results showed a significant increase of the P50 implicit time in schizophrenia patients compared with controls (t(55) = 2.1, p < .05, d = 0.55) and a significant increase of the N95 implicit time in schizophrenia patients compared with controls (t(55) = 4.2; p < .001, d = 0.66). We found an increased rod b-wave implicit time (dark-adapted 0.01 ERG) in the VH group compared to the AHNH group and to the control group, which was associated with lifetime VH score. Our results demonstrate a slowing of RGC signaling in schizophrenia patients, which could affect the quality of visual information reaching the visual cortex. The implications of the data for understanding VH in schizophrenia are discussed.

The role of the retina in visual hallucinations: A review of the literature and implications for psychosis.

Visual hallucinations are a psychotic symptom present in numerous clinical conditions such as eye disease, Parkinsonian syndromes, neurodegenerative disorders and psychosis. Alteration of low level visual processing is a common feature in these clinical conditions, and various stages of processing from the retina to visual cortices are involved. We undertook a literature review of abnormalities of the retina and their potential link with the occurrence of VHs in these clinical conditions of interest. We found that structural and functional abnormalities of the retina are frequently present. In Parkinson disease and eye disease, VHs have been related to dysfunctions of the retina. By contrast, in neurodegenerative disorders and psychosis, possible links have yet not been explored. We show that structural or functional abnormalities of the retina are given little consideration in cognitive models of VHs, which primarily postulate an alteration of sensory visual processing and a top-down attentional process. We conclude that contrast sensitivity measures and an exhaustive exploration of the retinal functions using the clinical electroretinography standards of the International Society for the Clinical Electrophysiology of Vision (ISCEV) are needed to explore retinal involvement in the occurrence of visual hallucinations.

Cognitive impairments in alcohol-dependent subjects.

Chronic excessive alcohol consumption induces cognitive impairments mainly affecting executive functions, episodic memory, and visuospatial capacities related to multiple brain lesions. These cognitive impairments not only determine everyday management of these patients, but also impact on the efficacy of management and may compromise the abstinence prognosis. Maintenance of lasting abstinence is associated with cognitive recovery in these patients, but some impairments may persist and interfere with the good conduct and the efficacy of management. It therefore appears essential to clearly define neuropsychological management designed to identify and evaluate the type and severity of alcohol-related cognitive impairments. It is also essential to develop cognitive remediation therapy so that the patient can fully benefit from the management proposed in addiction medicine units.

[Cognitive impairment of alcohol-dependent subjects]. / Troubles cognitifs du sujet alcoolodépendant.

Chronic excessive alcohol consumption induces multiple brain damages. Secondary cognitive disorders include executive functions, episodic memory and visuospatial capacities. The severity of these alcohol induced disorders may vary between sub-clinical manifestations (that may, nevertheless, interfere with medical management) and more important ones like Korsakoff syndrome or dementia. The latter are usually irreversible but many of these manifestations are potentially reversible with persistent abstinence. It therefore appears of particular importance to clearly define neuropsychological management in order to identify and evaluate the type and severity of alcohol-related cognitive disorders. The patients may then be offered rehabilitation for these cognitive impairments. This is the first step of a complete addiction program based especially on cognitive behavioral therapies.

Paradoxical state anxiety and working memory in a patient with acute stroke.

OBJECTIVE: In view of the negative impact of anxiety on working memory, we induced anxiety in 26 patients with acute stroke and 33 healthy controls, and studied how the anxiety affected their emotional reactivity and how the reactivity affected their verbal and visuospatial working memory. We compared the overall findings with those in 1 of our patients (C.B.) who had presented with an abnormally high level of state anxiety. METHODS: We gave verbal and visuospatial 1-back tasks under both neutral and anxiogenic conditions, and we compared participants' working memory scores, self-reported levels of state anxiety, and electrodermal activity. RESULTS: When comparing performance in the neutral condition, the control and patient groups exhibited disrupted verbal working memory, which was associated with greater electrodermal activity and higher state anxiety during the anxiogenic condition. Although patient C.B. also had heightened electrodermal activity during the anxiogenic condition, she experienced a significant reduction in her state anxiety. Her verbal working memory was better during the anxiogenic than the neutral condition. CONCLUSIONS: Because of the phonological (subvocal speech) nature of verbal working memory, a higher level of anxious apprehension could explain the increase in state anxiety and the corresponding disruption of verbal working memory in our patient and control groups during the anxiogenic condition. C.B.'s lower state anxiety and selective improvement in verbal working memory during the anxiogenic condition suggest that she felt less anxious apprehension.