Ruchika Gajwani

Attachment : developmental pathways to affective dysregulation in young people at ultra-high risk of developing psychosis

OBJECTIVE Embedded in attachment theory is its association with affect regulation, which provides a framework for affective dysregulation in the emerging psychosis. METHOD Fifty-one participants meeting criteria for ultra-high risk (UHR) of developing psychosis were recruited from a youth mental health service within the United Kingdom. At intake baseline, prior to starting therapeutic intervention, all clients were assessed on measures of affective dysregulation and attachment. RESULTS A large proportion of our sample (N = 51) reported clinically significant levels of depression (78%), state anxiety (59%), and social anxiety (65%). Eighty per cent of the UHR sample was insecurely attached. Insecure attachment was significantly associated with elevated depression and social anxiety. Attachment styles were associated with anxiety, depression, and social anxiety. There was no support for a mediating role of social anxiety between attachment styles and depression. CONCLUSION Clinically significant levels of distress and anxiety experienced by the young people at high risk of psychosis. Clinical implications for the treatment of affective dysregulation in young people at UHR in relation to their attachment styles have been discussed.

Predictors of engagement in first-episode psychosis

Engagement with psychiatric services is critical for ensuring successful outcomes in patients experiencing a first episode of psychosis (FEP). However, it is not known how sociodemographic factors and patient beliefs about the causes of mental illness affect engagement. This study explored predictors of engagement in a cohort of 103 FEP patients presenting to an early-intervention service. Beliefs that mental illness is caused by social stress or thinking odd thoughts predicted higher engagement scores. Patients with no qualifications were found to have higher engagement scores than those educated to a higher level. Ethnicity, gender, age and socioeconomic factors were not significantly correlated with engagement scores. Duration of untreated illness (DUI) significantly predicted higher engagement scores, but only for values >1220days. Duration of untreated psychosis (DUP) was not a significant predictor of patient engagement scores. Patient beliefs about the causes of mental illness are an important factor to be taken into consideration and may represent a target of interventions to increase engagement in FEP.

Does Quantitative Research in Child Maltreatment Tell the Whole Story? The Need for Mixed-Methods Approaches to Explore the Effects of Maltreatment in Infancy

Background and Aims. Research on child maltreatment has largely overlooked the under-five age group and focuses primarily on quantitative measurement. This mixed-methods study of maltreated children (N = 92) entering care (age 6–60 months) combines a quantitative focus on the associations between care journey characteristics and mental health outcomes with a qualitative exploration of maltreatment in four different families. Methods. Care journey data was obtained from social care records; mental health and attachment assessments were carried out following entry to care; qualitative data comprised semistructured interviews with professionals, foster carers, and parents. Results. Significant associations were found between suspected sexual abuse and increased DAI inhibited attachment symptoms (p = 0.001) and between reported domestic violence and decreased DAI inhibited (p = 0.016) and disinhibited (p = 0.004) attachment symptoms. Qualitative results: two themes demonstrate the complexity of assessing maltreatment: (1) overlapping maltreatment factors occur in most cases and (2) maltreatment effects may be particularly challenging to isolate. Conclusions. Qualitative exploration has underscored the complexity of assessing maltreatment, indicating why expected associations were not found in this study and posing questions for the quantitative measurement of maltreatment in general. We therefore suggest a new categorisation of maltreatment and call for the complimentary research lenses of further mixed-methods approaches.

Resting-state gamma-band power alterations in schizophrenia reveal E/I-balance abnormalities across illness-stages

We examined alterations in E/I-balance in schizophrenia (ScZ) through measurements of resting-state gamma-band activity in participants meeting clinical high-risk (CHR) criteria (n = 88), 21 first episode (FEP) patients and 34 chronic ScZ-patients. Furthermore, MRS-data were obtained in CHR-participants and matched controls. Magnetoencephalographic (MEG) resting-state activity was examined at source level and MEG-data were correlated with neuropsychological scores and clinical symptoms. CHR-participants were characterized by increased 64–90 Hz power. In contrast, FEP- and ScZ-patients showed aberrant spectral power at both low- and high gamma-band frequencies. MRS-data showed a shift in E/I-balance toward increased excitation in CHR-participants, which correlated with increased occipital gamma-band power. Finally, neuropsychological deficits and clinical symptoms in FEP and ScZ-patients were correlated with reduced gamma band-activity, while elevated psychotic symptoms in the CHR group showed the opposite relationship. The current study suggests that resting-state gamma-band power and altered Glx/GABA ratio indicate changes in E/I-balance parameters across illness stages in ScZ.

Using online-screening in the general population to detect participants at clinical high-risk for psychosis

Abstract Introduction Identification of participants at clinical high-risk (CHR) for the development of psychosis is an important objective of current preventive efforts in mental health research. However, the utility of using web-based screening approaches to detect CHR participants at the population level has not been investigated. Methods We tested a web-based screening approach to identify CHR individuals. Potential participants were invited to a website via e-mail invitations, flyers, and invitation letters involving both the general population and mental health services. Two thousand two hundred seventy-nine participants completed the 16-item version of the prodromal questionnaire (PQ-16) and a 9-item questionnaire of perceptual and cognitive aberrations (PCA) for the assessment of basic symptoms (BS) online. 52.3% of participants met a priori cut-off criteria for the PQ and 73.6% for PCA items online. One thousand seven hundred eighty-seven participants were invited for a clinical interview and n = 356 interviews were conducted (response rate: 19.9%) using the Comprehensive Assessment of At-Risk Mental State (CAARMS) and the Schizophrenia Proneness Interview, Adult Version (SPI-A). n = 101 CHR participants and n = 8 first-episode psychosis (FEP) were detected. ROC curve analysis revealed good to moderate sensitivity and specificity for predicting CHR status based on online results for both UHR and BS criteria (sensitivity/specificity: PQ-16 = 82%/46%; PCA = 94%/12%). Selection of a subset of 10 items from both PQ-16 and PCA lead to an improved of specificity of 57% while only marginally affecting sensitivity (81%). CHR participants were characterized by similar levels of functioning and neurocognitive deficits as clinically identified CHR groups. Conclusion These data provide evidence for the possibility to identify CHR participants through population-based web screening. This could be an important strategy for early intervention and diagnosis of psychotic disorders.

F159. NEUROMAGNETIC 40 HZ AUDITORY STEADY STATE RESPONSES AND AUDITORY CORTICAL GABA AND GLX IN CLINICAL HIGH RISK AND FIRST EPISODE OF PSYCHOSIS INDIVIDUALS

Abstract Background Robust impairments in the power and phase of 40 Hz auditory steady state responses (ASSR) have been reported in chronic schizophrenia patients. This could reflect changes in the balance between inhibitory GABAergic and excitatory glutamatergic neurotransmission in auditory cortex. However, the direct link between the ASSR and alterations in these neurotransmitter systems has not been systematically explored. Furthermore, it remains unclear whether 40 Hz ASSR impairments are present in early and at-risk stages of psychosis. The current study aims to explore the 40 Hz ASSR in first-episode of psychosis patients and individuals at clinical high risk (CHR) of psychosis, and the possible relationship of deficits in gamma-band entrainment to a dysfunctional excitation inhibition balance, as reflected by alterations in cortical GABA and glutamate. Methods Data from 80 CHR, 11 FEP and 40 age-matched healthy control participants were collected as part of the MRC-funded Youth Mental Health Risk and Resilience study. MEG data were recorded on a 4D Neuroimaging Magnes 3600 Whole Head 248 Channel system, while participants were passively presented with a series of 1000 Hz carrier tones amplitude modulated at 40 Hz. Data were analysed at sensor and source-level in the frequency-domain for spectral power and intertrial phase-coherence (ITPC). For source-reconstruction, an eLoreta source-analysis algorithms was employed. Auditory regions of interest (ROIs) were defined using 98 nodes defined from the AAL-atlas. Levels of right auditory GABA and Glx (glutamate + glutamine) were measured using 1H-MRS at 3T and 2*2*2 cm voxels and were estimated relative to water. GABA levels were further corrected for grey and white matter and cerebrospinal fluid levels within the voxel. Finally, 40 Hz ASSR power in right auditory cortex was explored in relation to neurotransmitter levels in the same region. Results Across groups, the ASSR stimulus activated temporal regions, including bilateral heschl’s gyrus and superior temporal cortex. A significant effect of hemisphere was found, reflecting higher 40 Hz ASSR power in the right hemisphere across groups. CHR and FEP participants showed attenuated 40 Hz ASSR power and ITPC compared to healthy control participants in right temporal regions, but an increase in spectral power in the left hemisphere. A moderate positive correlation was found between right auditory GABA and 40 Hz ASSR power in the right superior temporal gyrus in CHR, but not in controls. Discussion These results provide a link between MRS measures of GABA and 40 Hz ASSR power impairments in CHR individuals. Furthermore, these preliminary findings indicate that slight alterations in the 40 Hz ASSR are present in FEP patients and may arise already in the CHR stage, prior to the onset of psychosis.

S214. USING ONLINE-SCREENING TO DETECT PARTICIPANTS AT CLINICAL HIGH-RISK FOR PSYCHOSIS

Abstract Background Identification of participants at clinical high-risk (CHR) for the development of psychosis is an important objective of current preventive efforts in mental health research. However, the utility of using web-based screening approaches to detect CHR-participants at the population-level has not been investigated. Methods We tested a web-based screening approach to identify CHR-individuals. Potential participants were invited to a website via email-invitations, flyers and invitation letters involving both the general population and mental health services. 2121 participants completed the 16-item version of the prodromal questionnaire (PQ-16) and a 9-item questionnaire of perceptual and cognitive aberrations (PCA) for the assessment of Basic Symptoms (BS) online. Results 54% of participants met a-priori cut-off criteria for the PQ and 72 % for PCA-items online. 969 participants were invited for a clinical interview and n = 277 interviews were conducted (response rate: 29%) using the Comprehensive Assessment of At-Risk Mental State (CAARMS) and the Schizophrenia Proneness Interview, Adult Version (SPI-A). N = 88 CHR-participants and n = 8 first-episode psychosis (FEP) were detected. ROC-curve analysis revealed good to moderate sensitivity and specificity for predicting CHR-status based on online-results for both UHR- and BS-criteria (Sensitivity/Specificity: PQ-16 = 76%/50.4%; PCA = 89%/19.7%). CHR-participants were characterized by similar levels of functioning and neurocognitive deficits as clinically identified CHR-groups. Discussion These data provide evidence for the possibility to identify CHR-participants through population-based web-screening. This could be an important strategy for early intervention and diagnosis of psychotic disorders.

S42. KETAMINE DYSREGULATES TASK-RELATED NEURAL OSCILLATIONS IN THALAMO-CORTICAL CIRCUITS: IMPLICATIONS FOR PATHOPHYSIOLOGICAL THEORIES OF VISUAL-PERCEPTUAL DEFICITS IN SCHIZOPHRENIA

Abstract Background Hypofunction of the N-methyl-D-aspartate receptor (NMDA-R) has been implicated as a possible mechanism underlying cognitive deficits and aberrant neuronal dynamics in schizophrenia (ScZ). Methods In a single-blind cross-over design, 14 participants received either a subanaesthetic dose of S-ketamine (0.006 mg/Kg) or saline while Magnetoencephalographic (MEG) data were recorded during a visual task. In addition, MEG-data were obtained in a sample of unmedicated first-episode psychosis (FEP) patients (n = 10) and in patients with chronic ScZ (n = 16). MEG-data were analyzed at source-level in the 1–90 Hz frequency range in occipital and thalamic regions of interest (ROIs). In addition, directed functional connectivity analysis was performed using Granger Causality (GC). Psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS). Results Behavioral impairments were accompanied by increased amplitude and frequency of gamma-power (63–80 Hz) in occipital regions during Ketamine administration, while low-frequency (~5–30 Hz) activity was upregulated. Moreover, Ketamine disrupted feedforward (FF) and feedback (FB) signaling at high and low frequencies leading to hypoconnectivity in thalamo-cortical (TC) networks. In contrast, FEP and chronic ScZ patients showed a different pattern of MEG-activity, characterized by decreased task-induced high-gamma band oscillations and increased FF/FB-mediated GC-connectivity. Discussion The effects of Ketamine on high-frequency oscillations and their connectivity profile are not consistent with observations in FEP and chronic ScZ-patients. Accordingly, the current data have implications for theories of cognitive dysfunctions and circuit impairments in the disorder, suggesting that the effects of acute NMDA-R hypofunction are not consistent with impairments in visuo-perceptual oscillations in ScZ-patients.

F153. NEUROMAGNETIC MISMATCH NEGATIVITY IN CLINICAL HIGH RISK AND FIRST-EPISODE PSYCHOSIS INDIVIDUALS

Abstract Background Auditory mismatch negativity (MMN) and its magnetic counterpart (MMNm) are event-related potentials/fields elicited by violations of previously established auditory regularities (Näätänen et al. 2007). Reduced MMN amplitude is a robust finding in both medicated and unmedicated schizophrenia (ScZ) patients (for a review, see Umbricht & Krljes, 2005), potentially indicating impaired predictive processes (Sauer et al. 2017). Furthermore, several studies have examined MMN responses in individuals at clinical high risk for psychosis (CHR) and have found MMN deficits to be present already in this population, indicating that MMN is compromised before psychosis onset and could represent a marker of risk for psychosis development. However, not all studies have reported significant differences in MMN amplitude between clinical high risk and healthy individuals and there is evidence to suggest that MMN deficits are primarily observed in CHR individuals who transition to psychosis (Bodatsch et al., 2015). Methods The purpose of the present study is to investigate MEG recorded MMNm amplitude responses to both duration deviants and sound omissions in n = 90 CHR-individuals who were screened with the Schizophrenia Proneness Instrument and the Comprehensive Assessment of At Risk Mental States. N = 50 healthy controls served as a comparison group. We employed an auditory oddball paradigm in which three different sequences of auditory stimuli were presented binaurally at ~ 70 dB (150 ms SOA, 700 – 100 ms ISI). The standard sequence contained five identical tones (80 ms) and the deviant sequence contained four identical tones and one duration deviant tone (40 ms). In addition, an omission sequence which contained only four identical tones was included to examine auditory predictions. Participants were instructed to focus their attention away from the sounds and to perform a simple visual detection task. We analyzed MMNm responses to unpredictable deviant and omitted sounds in bsensor and source space. The linearly constrained minimum variance (LCMV) beamformer was used to identify the generators of the MMNm responses and to compute artefact-free source-level time-courses. Results Consistent with previous studies revealing MMN sources in auditory cortical areas, bilateral MMNm sources were localized in auditory cortices for both duration deviants and sound omissions. Our data show attenuated MMNm responses elicited by duration deviant sounds in CHR individuals compared to healthy controls. Discussion Taken together, the study findings suggest that reduced MMNm amplitude is present before psychosis onset and reflects aberrant predictive processing rather than deficient stimulus-specific adaptation. Clinical follow-up measurements will be obtained to determine whether MMNm amplitudes are a potential biomarker for predicting onset of psychosis.

Acute ketamine dysregulates task-related gamma-band oscillations in thalamo-cortical circuits in schizophrenia

NMDA receptor deficits have been implicated in schizophrenia. Grent-’t-Jong et al. show that treating healthy controls with ketamine triggers changes in neural oscillations during visual processing distinct from those seen in patients with schizophrenia. This suggests that acute NMDA receptor hypofunction does not account for visuo-perceptual deficits in the disorder.