The promise and challenges of transcranial magnetic stimulation and deep brain stimulation as therapeutic options for obsessive-compulsive disorder.

INTRODUCTION: Obsessive compulsive disorder (OCD) represents a complex and often difficult to treat disorder. Pharmacological and psychotherapeutic interventions are often associated with sub-optimal outcomes, and 40-60% of patients are resistant to first line therapies and thus left with few treatment options. OCD is underpinned by aberrant neurocircuitry within cortical, striatal, and thalamic brain networks. Considering the neurocircuitry impairments that underlie OCD symptomology, neurostimulation therapies provide an opportunity to modulate psychopathology in a personalized manner. Also, by probing pathological neural networks, enhanced understanding of disease states can be obtained. AREAS COVERED: This perspective discusses the clinical efficacy of TMS and DBS therapies, treatment access options, and considerations and challenges in managing patients. Recent scientific progress is discussed, with a focus on neurocircuitry and biopsychosocial aspects. Translational recommendations and suggestions for future research are provided. EXPERT OPINION: There is robust evidence to support TMS and DBS as an efficacious therapy for treatment resistant OCD patients supported by an excellent safety profile and favorable health economic data. Despite a great need for alternative therapies for chronic and severe OCD patients, resistance toward neurostimulation therapies from regulatory bodies and the psychiatric community remains. The authors contend for greater access to TMS and DBS for treatment resistant OCD patients at specialized sites with appropriate clinical resources, particularly considering adjunct and follow-up care. Also, connectome targeting has shown robust predictive ability of symptom improvements and holds potential in advancing personalized neurostimulation therapies.

Neuroimaging Insights: Kava's (Piper methysticum) Effect on Dorsal Anterior Cingulate Cortex GABA in Generalized Anxiety Disorder.

Generalised Anxiety Disorder (GAD) is a prevalent, chronic mental health disorder. The measurement of regional brain gamma-aminobutyric acid (GABA) offers insight into its role in anxiety and is a potential biomarker for treatment response. Research literature suggests Piper methysticum (Kava) is efficacious as an anxiety treatment, but no study has assessed its effects on central GABA levels. This study investigated dorsal anterior cingulate (dACC) GABA levels in 37 adult participants with GAD. GABA was measured using proton magnetic resonance spectroscopy (1H-MRS) at baseline and following an eight-week administration of Kava (standardised to 120 mg kavalactones twice daily) (n = 20) or placebo (n = 17). This study was part of the Kava for the Treatment of GAD (KGAD; ClinicalTrials.gov: NCT02219880), a 16-week intervention study. Compared with the placebo group, the Kava group had a significant reduction in dACC GABA (p = 0.049) at eight weeks. Baseline anxiety scores on the HAM-A were positively correlated with GABA levels but were not significantly related to treatment. Central GABA reductions following Kava treatment may signal an inhibitory effect, which, if considered efficacious, suggests that GABA levels are modulated by Kava, independent of reported anxiety symptoms. dACC GABA patterns suggest a functional role of higher levels in clinical anxiety but warrants further research for symptom benefit. Findings suggest that dACC GABA levels previously un-examined in GAD could serve as a biomarker for diagnosis and treatment response.

Effects of Yoga and Aerobic Exercise on Verbal Fluency in Physically Inactive Older Adults: Randomized Controlled Trial (FitForAge).

Purpose: To compare the effects on verbal fluency of a supported yoga-based exercise intervention to an aerobic exercise intervention and a wait-list control group. Participants and Methods: Eighty-two physically-inactive but otherwise healthy adults (mean age 72.5 years, range 65-85, 77% female) were recruited into a 12-week, three-group, parallel randomized controlled trial. Participants were supported to complete ≥3 Hatha yoga classes per/week or ≥3 structured aerobic exercise sessions/week. A wait-list control group continued usual daily activities only. Verbal fluency, including total-FAS, animals, and verbs, was assessed before and after interventions. Group effects were assessed using analysis of covariance (ANCOVA). Results: Twenty-seven participants were randomized to yoga, 29 to aerobic exercise and 26 to a waitlist. At 12-week follow-up, compared to baseline, there were increases in mean total-FAS in the yoga (+5.0 words, p=0.002) and aerobic exercise groups (+6.6 words, p=0.004). Mean total-FAS in the wait-list control group remained stable (-0.5 words, p=0.838). There were medium-magnitude estimated treatment effects on total-FAS for yoga versus wait-list control and aerobic exercise versus wait-list control: Hedges' g=0.51 (p=0.213) and 0.57 (p=0.098) respectively. In addition, small-to-medium magnitude estimated treatment effects were seen on animals and verbs for yoga versus wait-list control and aerobic exercise versus wait-list control: g=0.28 (p=0.155), 0.19 (p=0.766) and 0.50 (p=0.085), 0.59 (p=0.233) respectively. Conclusion: Participation in yoga or aerobic exercise was associated with estimated improvements in verbal fluency compared to a non-active control group. Yoga and aerobic exercise may be promising approaches by which to promote cognitive function among older adults. Trial Registration: DRKS00015093, U1111-1217-4248.

Mindfulness, mood symptom tendencies and quality of life in bipolar disorder: An examination of the mediating influence of emotion regulation difficulties.

BACKGROUND: The aim of this cross-sectional study was to investigate dispositional mindfulness and its association with depression and manic tendencies, and subjective life quality in bipolar disorder (BD). Furthermore, this study sought to examine the potential mediating effects of emotion regulation difficulties on these relationships. METHOD: Twenty-eight healthy controls (HC) and 66 clinically stable outpatients with a DSM-IV-TR diagnosis of BD completed the Mindfulness Attention Awareness Scale (MAAS), Difficulties in Emotion Regulation Scale (DERS), Seven Up (7 Up) Seven Down (7 Down) and the Quality of Life in Bipolar Disorder Questionnaire (QoL.BD). These variables were compared between groups and entered into a series of mediation analyzes using PROCESS in the BD group only. RESULTS: Lower MAAS scores were detected amongst the BD patients compared to HCs. Lower MAAS scores in BD patients predicted higher 7 Up, 7 Down and lower QoL.BD scores. For the 7 Down and QoL.BD, the associations were completely mediated by DERS scores, with difficulties in strategy use and emotional clarity mediating the association between mindfulness and depressive tendencies and quality of life, respectively. No significant direct or indirect effects were detected for the 7 Up model. LIMITATIONS: The cross-sectional design precludes causal inference. The MAAS conceptualises mindfulness as unidimensional. Self-report scales of depressive and manic tendencies utilised. CONCLUSIONS: This study detected a significant association between dispositional mindfulness and depressive tendencies and life quality in BD, and found that these associations were influenced by emotion regulation difficulties. These findings encourage further investigation of mindfulness-based interventions in BD.

Medicinal psychedelics for mental health and addiction: Advancing research of an emerging paradigm.

The medical use of psychedelic substances (e.g. psilocybin, ayahuasca, lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine) is attracting renewed interest, driven by a pressing need for research and development of novel therapies for psychiatric disorders, as well as promising results of contemporary studies. In this Viewpoint, we reflect upon the 'Clinical Memorandum on Psychedelics' recently released by the Royal Australian and New Zealand College of Psychiatrists and note subsequent developments including the application for down-scheduling of psilocybin and 3,4-methylenedioxymethamphetamine presently being considered by the Therapeutic Goods Administration and approvals for access via the Special Access Scheme. We suggest that this field is worthy of rigorous research to assess potential benefits, address safety parameters and clarify therapeutic mechanisms. To this end, we outline recent research findings, provide an overview of current knowledge relating to mechanisms of action and discuss salient aspects of the psychedelic-assisted psychotherapy treatment model. The sum of this research points towards medicinal psychedelics as a potential new class of psychiatric treatments when used within a medically supervised framework with integrated psychotherapeutic support. However, before widespread translation into clinical use can occur, appropriately designed and sufficiently powered trials are required to detect both potential positive and negative outcomes. Unique safety and regulatory challenges also need to be addressed. As for any new medical therapy, psychedelic research needs to be conducted in a rigorous manner, through the dispassionate lens of scientific enquiry. Carte blanche availability to practitioners, without specific protocols and appropriate training, would be potentially harmful to individuals and detrimental to the field.

Meta-analysis of randomised controlled trials with N-acetylcysteine in the treatment of schizophrenia.

OBJECTIVE: There is accumulating evidence that adjunctive treatment with N-acetylcysteine may be effective for schizophrenia. This study aimed to conduct a comprehensive meta-analysis examining the efficacy of randomised control trials investigating N-acetylcysteine as an adjunct treatment for schizophrenia and the first to investigate cognition as an outcome. METHODS: We systematically reviewed Medline, EmCare, PsycINFO, Embase, CINAHL Complete, China Knowledge Resource Integrated Database and the Cochrane Clinical Trials online registry for randomised control trials of N-acetylcysteine for schizophrenia. We undertook pairwise meta-analyses of N-acetylcysteine vs placebo for psychosis symptoms and cognition. RESULTS: Seven studies, including n = 220 receiving N-acetylcysteine and n = 220 receiving placebo, met inclusion criteria for the pairwise meta-analyses. Positive and Negative Syndrome Scale negative and total scores were significantly improved in the N-acetylcysteine group after 24 weeks of treatment. The cognitive domain of working memory improved with N-acetylcysteine supplementation. CONCLUSION: Evidence supports the notion that N-acetylcysteine may be a useful adjunct to standard treatment for the improvement of schizophrenia symptoms, as well as the cognitive domain of working memory. Treatment effects were observed at the later time point (⩾24 weeks), suggesting that longer interventions are required for the success of N-acetylcysteine treatment.

The Acceptability, Feasibility and Potential Outcomes of an Individual Mindfulness-Based Intervention for Hearing Voices.

BACKGROUND: A prominent area of advancement in the psychological treatment for people with persisting psychosis has been the application of mindfulness-based therapies. Recent literature has recommended the investigation of focused mindfulness interventions for voices (auditory hallucinations) as a specific experience. To date, only mindfulness programs in group format have been examined. AIMS: This non-randomized pilot study aimed to assess the acceptability, feasibility and potential outcomes of an individual mindfulness program for persistent voices on the negative impact of voices on the subjective experience of mental health and wellbeing, depression and voice-related distress and disruption. Also, it aimed to identify potential psychological and neurocognitive mechanisms of change. METHOD: A new 4-week individual Mindfulness Program for Voices (iMPV) was developed, and piloted with a group of 14 participants with a schizophrenia-spectrum disorder and persisting voices. Participants completed clinical and neurocognitive measures pre- and post-intervention and at 2-month follow-up. RESULTS: Results revealed low attrition rates, high formal practice engagement levels and positive participant feedback. Pre-post outcomes suggested small to moderate effects for a reduction in the negative impact of voices on experience, depression and disruption. Large effects for changes in mindful responding and attentional switching were also identified. CONCLUSIONS: Our findings suggest that this novel treatment protocol is appropriate, engaging and safe for persistent voice hearers. Findings for mindful responding and attentional switching suggest these to be potential mechanisms of change for further investigation. Further RCTs are warranted to ascertain the feasibility and efficacy for focused mindfulness interventions for voices of individual format.

Exploring the relationship between fantasy proneness and delusional beliefs in psychosis and non-clinical individuals.

Delusions are a core feature of psychopathology while fantasy proneness (FP) is a trait that describes a predisposition towards fantastical thinking, vivid mental imagery and an overactive imagination. The relationship between FP and delusional experiences has not yet been examined in the literature. The current study hypothesised that FP would be significantly associated with and predict delusion severity as well as the associated delusional distress, preoccupation and conviction. Ninety-five patients with current psychosis (schizophrenia and bipolar I disorder) were assessed for overall delusional severity using the PANSS (clinician-rated) and the Peters Delusions Inventory (PDI; self-report). FP was assessed using the Creative Experiences Questionnaire (CEQ). Forty-six healthy control participants also completed the PDI and CEQ. Significant positive correlations were observed between FP and delusion severity in both groups; and distress, preoccupation and conviction in patients only. Linear regression analyses, controlling for manic and depressive symptoms, revealed that greater FP predicted higher levels of severity, distress, preoccupation, and conviction associated with delusions in patients, and higher severity only in healthy controls. The findings highlight the role of specific cognitive biases in delusional experiences, and empirically support models of unusual belief formation and maintenance.

Mindfulness- and acceptance-based interventions for psychosis: Our current understanding and a meta-analysis.

In promoting optimal recovery in persons with psychosis, psychological interventions have become a key element of treatment, with cognitive behavioural therapy being widely recommended in clinical practice guidelines. One key area of development has been the trialling of "third wave" cognitive behavioural interventions, which promote mindfulness, acceptance and compassion as means of change. Trials to date have demonstrated encouraging findings, with beneficial effects observed on measures of psychotic symptoms. This meta-analysis evaluated the efficacy of third wave interventions for the treatment of psychosis in randomised controlled trials, with psychotic symptoms as the primary outcome. Overall, 10 studies were included. The primary outcome demonstrated a small but significant effect (g=0.29) for third wave interventions compared with control post-treatment. Trials of group format mindfulness-based interventions showed larger effects (g=0.46) than individual acceptance and commitment therapy based interventions (g=0.08), although methodological differences between trials were noted. Among secondary outcomes, a moderate, significant treatment effect (g=0.39) was found for depressive symptoms, but no significant effects were found on specific measures of positive and negative symptoms, hallucination distress, or functioning/disability. A moderate effect on mindfulness (g=0.56) was observed, but not on acceptance. Overall, findings indicate that third wave interventions show beneficial effects on symptoms in persons with psychotic disorders. However, further research is required to determine the efficacy of specific models of treatment.

Face and Object Perception in Body Dysmorphic Disorder versus Obsessive-Compulsive Disorder: The Mooney Faces Task.

OBJECTIVES: Body dysmorphic disorder (BDD) is characterized by repetitive behaviors and/or mental acts occurring in response to preoccupations with perceived defects or flaws in physical appearance. There are some similarities, but also important differences, between BDD and obsessive-compulsive disorder (OCD), not just in terms of core clinical symptoms, but possibly in the domain of perception. This study compared the nature and extent of perceptual anomalies in BDD versus OCD and health controls (HC), using a modified Mooney task. METHODS: We included 21 BDD, 19 OCD, and 21 HC participants, who were age-, sex-, and IQ-matched. A set of 40 Mooney faces and 40 Mooney objects arranged in three configurations (i.e., upright, inverted, or scrambled) were presented under brief (i.e., 500 ms) free-viewing conditions. Participants were asked to decide whether each image represented a human face, an object, or neither in a forced-choice paradigm. RESULTS: The BDD group showed significantly reduced face and object inversion effects relative to the other two groups. This was accounted for by BDD participants being significantly more accurate in identifying inverted Mooney faces and objects than the other participants. CONCLUSIONS: These data were interpreted as reflecting an overreliance on independent components at the expense of holistic (configural) processing in BDD. (JINS, 2017, 23, 471-480).

Multimodal emotion integration in bipolar disorder: an investigation of involuntary cross-modal influences between facial and prosodic channels.

The ability to integrate information from different sensory channels is a vital process that serves to facilitate perceptual decoding in times of unimodal ambiguity. Despite its relevance to psychosocial functioning, multimodal integration of emotional information across facial and prosodic modes has not been addressed in bipolar disorder (BD). In light of this paucity of research we investigated multimodal processing in a BD cohort using a focused attention paradigm. Fifty BD patients and 52 healthy controls completed a task assessing the cross-modal influence of emotional prosody on facial emotion recognition across congruent and incongruent facial and prosodic conditions, where attention was directed to the facial channel. There were no differences in multi-modal integration between groups at the level of accuracy, but differences were evident at the level of response time; emotional prosody biased facial recognition latencies in the control group only, where a fourfold increase in response times was evident between congruent and incongruent conditions relative to patients. The results of this study indicate that the automatic process of integrating multimodal information from facial and prosodic sensory channels is delayed in BD. Given that interpersonal communication usually occurs in real time, these results have implications for social functioning in the disorder.

Regional brain volumes in body dysmorphic disorder compared to controls.

OBJECTIVES: Body dysmorphic disorder (BDD) is characterized by a preoccupation with a misperceived flaw in appearance, causing significant distress and disability. Neuropsychological research has revealed deficits in executive function and inhibitory control of emotional responses. The few previous structural neuroimaging studies have had inconclusive findings and we aimed to take this field of research forward by contributing high quality structural data. METHODS: To investigate regional brain volumes we compared 20 BDD participants and 20 matched controls using high-resolution structural T1-weighted magnetic resonance imaging (MRI). The MRI data was subjected to cortical reconstruction and volumetric segmentation using Freesurfer software. RESULTS: Results showed the right orbitofrontal cortex, bilateral thalamus, left anterior cingulate cortex, hippocampus and amygdala were significantly smaller in the BDD sample compared to controls. The most pronounced differences were in the right orbitofrontal cortex and left anterior cingulate cortex, as these areas were smaller in BDD participants independent of reduced global brain volumes. Duration of illness significantly negatively correlated with right orbitofrontal cortex volumes. CONCLUSIONS: This is the largest volumetric neuroimaging study in BDD to date and provides important data on volumetric differences that implicate fronto-limbic circuits.

Auditory processing and hallucinations in schizophrenia.

The aim of this study was to investigate whether deficits in auditory processing are associated with auditory hallucinations in patients with schizophrenia. It was hypothesised that individuals with a diagnosis of schizophrenia would demonstrate deficits in processing the spectral and temporal aspects of sound and that such deficits would be more pronounced in patients with a history of auditory hallucinations (hallucinators) than those without such a history (non-hallucinators). A community sample meeting clinical criteria for schizophrenia or schizoaffective disorder (19 hallucinators, 15 non-hallucinators) and a matched healthy control group (n=17) completed a broad range of auditory processing tasks involving pitch discrimination of modulated (temporal) and unmodulated (spectral) pure tones, auditory streaming and affective prosodic identification, as well as measures assessing current psychiatric symptoms. In all experimental tasks patients were impaired compared to controls. Specifically hallucinators performed worse than non-hallucinators and controls for pitch discrimination of unmodulated tones and auditory streaming, and both hallucinators and non-hallucinators performed significantly worse than controls for discrimination of modulated tones and affective prosody. These findings suggest that impaired temporal processing may contribute to general difficulties identifying affective speech prosody in patients with schizophrenia, while spectral processing deficits may specifically compromise melodic streaming in hallucinators, which combined with deficits in temporal processing, contribute to the experience of auditory hallucinations.

Gender differences in prepulse inhibition (PPI) in bipolar disorder: men have reduced PPI, women have increased PPI.

Prepulse inhibition (PPI) is a measure of sensorimotor gating or information processing. Few studies have examined PPI in bipolar disorder (BD); two studies reported a PPI disruption and two reported no change. There are gender differences in PPI and within the clinical profile of BD, which may explain some of these discrepancies. Thus, the effect of gender on PPI in BD was the focus of the current study. Euthymic BD patients (14 male/15 female) were compared to age- and IQ-matched healthy control participants (16 male/16 female). Assessment of PPI included 21 pulse-alone trials (115 dB) and a total of 42 prepulse-pulse trials (seven of each prepulse: 74, 78, 86 dB) at two stimulus onset asynchrony levels (SOA: 60, 120 ms). There was a group x SOA and a group x gender interaction, reflecting that men with BD showed reduced PPI compared to control males at the 60-ms SOA (3% in BD vs. 26% in controls), but not the 120-ms SOA. In contrast, women with BD had significantly increased PPI compared to female controls at the 120-ms SOA (49% in BD vs. 29% in controls), but not the 60-ms SOA. Compared to control participants BD patients showed changes in PPI, which are gender-dependent; male BD participants had reduced PPI, whereas female BD participants had increased PPI. This gender difference highlights the need to consider men and women with BD as two distinct groups, at least in PPI studies.