A qualitative study of the acceptability of cognitive bias modification for paranoia (CBM-pa) in patients with psychosis.

BACKGROUND: Cognitive Bias Modification (CBM) has been used successfully as a computer-based intervention in disorders such as anxiety. However, CBM to modify interpretations of ambiguous information relevant to paranoia has not yet been tested. We conducted a qualitative investigation of a novel intervention called CBM for paranoia (CBM-pa) to examine its acceptability in patients with psychosis. METHODS: Eight participants with psychosis who completed CBM-pa were identified by purposive sampling and invited for a semi-structured interview to explore the facilitators and barriers to participation, optimum form of delivery, perceived usefulness of CBM-pa and their opinions on applying CBM-pa as a computerised intervention. The interviews were transcribed and analysed using thematic analysis by researchers working in collaboration with service users. RESULTS: Themes emerged relating to participants' perception about delivery, engagement, programme understanding, factors influencing experience, perceived impact and application of CBM-pa. CBM-pa was regarded as easy, straightforward and enjoyable. It was well-accepted among those we interviewed, who understood the procedure as a psychological intervention. Patients reported that it increased their capacity for adopting alternative interpretations of emotionally ambiguous scenarios. Although participants all agreed on the test-like nature of the current CBM-pa format, they considered that taking part in sessions had improved their overall wellbeing. Most of them valued the computer-based interface of CBM-pa but favoured the idea of combining CBM-pa with some form of human interaction. CONCLUSIONS: CBM-pa is an acceptable intervention that was well-received by our sample of patients with paranoia. The current findings reflect positively on the acceptability and experience of CBM-pa in the target population. Patient opinion supports further development and testing of CBM-pa as a possible adjunct treatment for paranoia. TRIAL REGISTRATION: Current Controlled Trials ISRCTN: 90749868 . Retrospectively registered on 12 May 2016.

Salience attribution and its relationship to cannabis-induced psychotic symptoms.

BACKGROUND: Cannabis is a widely used drug associated with increased risk for psychosis. The dopamine hypothesis of psychosis postulates that altered salience processing leads to psychosis. We therefore tested the hypothesis that cannabis users exhibit aberrant salience and explored the relationship between aberrant salience and dopamine synthesis capacity. METHOD: We tested 17 cannabis users and 17 age- and sex-matched non-user controls using the Salience Attribution Test, a probabilistic reward-learning task. Within users, cannabis-induced psychotic symptoms were measured with the Psychotomimetic States Inventory. Dopamine synthesis capacity, indexed as the influx rate constant K i cer , was measured in 10 users and six controls with 3,4-dihydroxy-6-[18F]fluoro-l-phenylalanine positron emission tomography. RESULTS: There was no significant difference in aberrant salience between the groups [F 1,32 = 1.12, p = 0.30 (implicit); F 1,32 = 1.09, p = 0.30 (explicit)]. Within users there was a significant positive relationship between cannabis-induced psychotic symptom severity and explicit aberrant salience scores (r = 0.61, p = 0.04) and there was a significant association between cannabis dependency/abuse status and high implicit aberrant salience scores (F 1,15 = 5.8, p = 0.03). Within controls, implicit aberrant salience was inversely correlated with whole striatal dopamine synthesis capacity (r = -0.91, p = 0.01), whereas this relationship was non-significant within users (difference between correlations: Z = -2.05, p = 0.04). CONCLUSIONS: Aberrant salience is positively associated with cannabis-induced psychotic symptom severity, but is not seen in cannabis users overall. This is consistent with the hypothesis that the link between cannabis use and psychosis involves alterations in salience processing. Longitudinal studies are needed to determine whether these cognitive abnormalities are pre-existing or caused by long-term cannabis use.

Measuring endogenous changes in serotonergic neurotransmission in humans: a [11C]CUMI-101 PET challenge study.

Serotonin (5-HT) neurotransmission is implicated in cognitive and emotional processes and a number of neuropsychiatric disorders. The use of positron emission tomography (PET) to measure ligand displacement has allowed estimation of endogenous dopamine release in the human brain; however, applying this methodology to assess central 5-HT release has proved more challenging. The aim of this study was to assess the sensitivity of a highly selective 5-HT(1A) partial agonist radioligand [(11)C]CUMI-101 to changes in endogenous 5-HT levels induced by an intravenous challenge with the selective 5-HT re-uptake inhibitor (SSRI), citalopram, in healthy human participants. We studied 15 healthy participants who underwent PET scanning in conjunction with [(11)C]CUMI-101 after receiving an intravenous infusion of citalopram 10 mg or placebo in a double-blind, crossover, randomized design. Regional estimates of binding potential (BP(ND)) were obtained by calculating total volumes of distribution (V(T)) for presynaptic dorsal raphe nucleus (DRN) and postsynaptic cortical regions. Relative to placebo, citalopram infusion significantly increased [(11)C]CUMI-101 BP(ND) at postsynaptic 5-HT(1A) receptors in several cortical regions, but there was no change in binding at 5-HT(1A) autoreceptors in the DRN. Across the postsynaptic brain regions, citalopram treatment induced a mean 7% in [(11)C]CUMI-101 BP(ND) (placebo 1.3 (0.2); citalopram 1.4 (0.2); paired t-test P=0.003). The observed increase in postsynaptic [(11)C]CUMI-101 availability identified following acute citalopram administration could be attributable to a decrease in endogenous 5-HT availability in cortical terminal regions, consistent with preclinical animal studies, in which acute administration of SSRIs decreases DRN cell firing through activation of 5-HT(1A) autoreceptors to reduce 5-HT levels in postsynaptic regions. We conclude that [(11)C]CUMI-101 may be sensitive to changes in endogenous 5-HT release in humans.

Electrophysiological correlates of masked face priming.

Using a sandwich-masked priming paradigm with faces, we report two ERP effects that appear to reflect different levels of subliminal face processing. These two ERP repetition effects dissociate in their onset, scalp topography, and sensitivity to face familiarity. The "early" effect occurred between 100 and 150 ms, was maximally negative-going over lateral temporoparietal channels, and was found for both familiar and unfamiliar faces. The "late" effect occurred between 300 and 500 ms, was maximally positive-going over centroparietal channels, and was found only for familiar faces. The early effect resembled our previous fMRI data from the same paradigm; the late effect resembled the behavioural priming found, in the form of faster reaction times to make fame judgments about primed relative to unprimed familiar faces. None of the ERP or behavioural effects appeared explicable by a measure of participants' ability to see the primes. The ERP and behavioural effects showed some sensitivity to whether the same or a different photograph of a face was repeated, but could remain reliable across different photographs, and did not appear attributable to a low-level measure of pixelwise overlap between prime and probe photograph. The functional significance of these ERP effects is discussed in relation to unconscious perception and face processing.

Effect of spatial attention on stimulus-specific haemodynamic repetition effects.

The aim of this fMRI study was to investigate whether spatial attention to the initial and/or repeated presentation of a stimulus is necessary to observe repetition-related modulations of the neural responses evoked by that stimulus. During each trial, two stimuli were presented simultaneously, one left and one right of fixation. During each block, participants were instructed to attend covertly to stimuli in one of the two hemifields and respond whether each was a face or house, ignoring the contralateral stimulus. Regions that preferred one stimulus category over the other, such as the fusiform face area and parahippocampal place area, showed evidence of some processing of the ignored stimuli. However, a reduced response to repeated stimuli (repetition suppression) was only reliable for preferred stimuli when both their initial and repeated presentations were attended. This suggests that attention is necessary for both the acquisition and expression of the neural mechanisms that underlie repetition suppression, at least over the lags of 2-16 intervening trials used here.