Clinical outcomes of deep brain stimulation for obsessive-compulsive disorder: Insight as a predictor of symptom changes.

AIM: Deep brain stimulation (DBS) is a safe and effective treatment option for people with refractory obsessive-compulsive disorder (OCD). Yet our understanding of predictors of response and prognostic factors remains rudimentary, and long-term comprehensive follow-ups are lacking. We aim to investigate the efficacy of DBS therapy for OCD patients, and predictors of clinical response. METHODS: Eight OCD participants underwent DBS stimulation of the nucleus accumbens (NAc) in an open-label longitudinal trial, duration of follow-up varied between 9 months and 7 years. Post-operative care involved comprehensive fine tuning of stimulation parameters and adjunct multidisciplinary therapy. RESULTS: Six participants achieved clinical response (35% improvement in obsessions and compulsions on the Yale Brown Obsessive Compulsive Scale (YBOCS)) within 6-9 weeks, response was maintained at last follow up. On average, the YBOCS improved by 45% at last follow up. Mixed linear modeling elucidated directionality of symptom changes: insight into symptoms strongly predicted (P = 0.008) changes in symptom severity during DBS therapy, likely driven by initial changes in depression and anxiety. Precise localization of DBS leads demonstrated that responders most often had their leads (and active contacts) placed dorsal compared to non-responders, relative to the Nac. CONCLUSION: The clinical efficacy of DBS for OCD is demonstrated, and mediators of changes in symptoms are proposed. The symptom improvements within this cohort should be seen within the context of the adjunct psychological and biopsychosocial care that implemented a shared decision-making approach, with flexible iterative DBS programming. Further research should explore the utility of insight as a clinical correlate of response. The trial was prospectively registered with the ANZCTR (ACTRN12612001142820).

Diagnostic agreement and concordance between consultation-liaison psychiatry and non-psychiatric (medical and surgical) doctors: changes within junior doctor's terms.

OBJECTIVE: To investigate whether diagnostic agreement and concordance between non-psychiatric (medical and surgical) doctors and consultation-liaison psychiatry changes within junior doctors' terms. METHOD: This was a retrospective cohort analysis of referrals from medical and surgical units to a consultation-liaison psychiatry service. Diagnostic agreement was calculated across all diagnoses and expressed as a percentage. Diagnostic concordance (expressed using Cohen's Kappa) was calculated for the two most common diagnoses of depression and delirium. Diagnostic agreement and concordance in the first two weeks (Timepoint A) were compared to those in the last two weeks (Timepoint B) of junior doctors' terms. RESULTS: Around half the referrals (Timepoint A = 48.1%, Timepoint B = 54.0%) were excluded as no diagnosis was listed.Diagnostic agreement over all diagnoses was 31.7% (Timepoint A) and 29.9% (Timepoint B) and was not statistically different. Diagnostic concordance for depression increased from fair to moderate but was not statistically significant. Diagnostic concordance for delirium was substantial for both timepoints and were not statistically different. CONCLUSIONS: No statistically significant change in diagnostic accuracy over a junior doctors' term was found in this study.

Resting-state functional brain networks in first-episode psychosis: A 12-month follow-up study.

INTRODUCTION: Schizophrenia is increasingly conceived as a disorder of brain network connectivity and organization. However, reports of network abnormalities during the early illness stage of psychosis are mixed. This study adopted a data-driven whole-brain approach to investigate functional connectivity and network architecture in a first-episode psychosis cohort relative to healthy controls and whether functional network properties changed abnormally over a 12-month period in first-episode psychosis. METHODS: Resting-state functional connectivity was performed at two time points. At baseline, 29 first-episode psychosis individuals and 30 healthy controls were assessed, and at 12 months, 14 first-episode psychosis individuals and 20 healthy controls completed follow-up. Whole-brain resting-state functional connectivity networks were mapped for each individual and analyzed using graph theory to investigate whether network abnormalities associated with first-episode psychosis were evident and whether functional network properties changed abnormally over 12 months relative to controls. RESULTS: This study found no evidence of abnormal resting-state functional connectivity or topology in first-episode psychosis individuals relative to healthy controls at baseline or at 12-months follow-up. Furthermore, longitudinal changes in network properties over a 12-month period did not significantly differ between first-episode psychosis individuals and healthy control. Network measures did not significantly correlate with symptomatology, duration of illness or antipsychotic medication. CONCLUSIONS: This is the first study to show unaffected resting-state functional connectivity and topology in the early psychosis stage of illness. In light of previous literature, this suggests that a subgroup of first-episode psychosis individuals who have a neurotypical resting-state functional connectivity and topology may exist. Our preliminary longitudinal analyses indicate that there also does not appear to be deterioration in these network properties over a 12-month period. Future research in a larger sample is necessary to confirm our longitudinal findings.

Cognitive existential couple therapy (CECT) in men and partners facing localised prostate cancer: a randomised controlled trial.

OBJECTIVES: To assess the efficacy of cognitive existential couple therapy (CECT) for relationship function, coping, cancer distress and mental health in men with localised prostate cancer and in their partners. PATIENTS SUBJECTS AND METHODS: A randomised controlled trial was conducted with 62 couples randomly assigned to the six-session CECT programme or care as usual. The couple's relationship function (primary outcome), and coping, cancer distress and mental health (secondary outcomes) were evaluated at T0 (baseline), T1 (after treatment) and T2 (9 months from T0). A repeated-measures analysis of covariance model, which incorporated T0 measurements as a covariate, was used to compare treatment groups at T1 and T2. RESULTS: After CECT, patients reported significantly greater use of adaptive coping (P = 0.03) and problem-focused coping (P = 0.01). These gains were maintained at follow-up, while relationship cohesion had improved (P = 0.03), as had relationship function for younger patients (P = 0.01). Younger partners reported less cancer-specific distress (P = 0.008), avoidance (P = 0.04), intrusive thought (P = 0.006), and hyperarousal (P = 0.01). Gains were maintained at follow-up, while relationship cohesion (P = 0.007), conflict resolution (P = 0.01) and relational function (P = 0.009) all improved. CONCLUSION: CECT resulted in improved coping for patients and lower cancer-distress for partners. Maintained over time this manifests as improved relationship function. CECT was acceptable to couples, alleviated long-term relationship decline, and is therefore suitable as a preventative mental health intervention for couples facing prostate cancer. Given resourcing demands, we recommend dissemination of CECT be targeted at younger couples, as CECT was more acceptable to the younger group, and they derived greater benefit from it.

Joint hypermobility in functional neurological disorder: A cross-sectional study.

BACKGROUND: Functional Neurological Disorder (FND) is associated with anxiety and depression, and perhaps with joint hypermobility, which is itself associated with anxiety and depression. We conducted a survey to explore the relationship between these. METHODS: An online survey of people with FND was conducted, with participants asked to nominate healthy controls from their social group to join. Participants were asked about their anxiety (measured with GAD7), depression (measured with PHQ9) and joint hypermobility (measured with 5PQ). A regression analysis was conducted using a general linear model. RESULTS: 215 people with FND and 22 people without FND were included in the analysis. GAD7, PHQ9 and hypermobility scores were all higher in the group with FND, with 74% of people with FND meeting the common cut-off for a diagnosis of joint hypermobility syndrome, as compared with 45% of those without FND. Anxiety, depression and joint hypermobility scores all predicted FND status, with joint hypermobility the strongest. Hypermobility moderated the effect of anxiety, with the effect being stronger at lower levels of anxiety. CONCLUSION: While anxiety, depression and hypermobility symptoms each appear to contribute to FND, the role of anxiety is moderated by hypermobility, particularly when anxiety is lower.

Depression and physical illness.

Depressive symptoms frequently accompany physical illness, but the association between the two is complex. The combination has detrimental implications for the patient's health outcome, quality of life, medical treatment and health care use. The presence of physical symptoms of the medical illness can lead to challenges in recognising and diagnosing depression. This is best dealt with by placing greater emphasis on the psychological symptoms of depression. Recognition may be improved through use of appropriate screening tools for depression in medically ill patients. The management of depression in the setting of medical illness involves both general and specific approaches. General approaches include optimal treatment of the medical illness, exclusion of treatments that are associated with depressive symptoms, and simple general health strategies aimed at improving sleep and exercise. Good evidence exists for selective psychotherapeutic approaches and antidepressant treatments, but care is required to avoid drug-drug and illness-drug interactions with the latter.

Functional somatic syndromes and joint hypermobility: A systematic review and meta-analysis.

OBJECTIVE: There have been multiple reports of increased joint hypermobility (JH) in functional somatic syndromes (FSS). We sought to evaluate the evidence for an association. METHODS: A systematic search of the databases Medline and PsycINFO was conducted to identify all controlled studies from inception to February 2020 measuring the association of an FSS and JH. Records were identified and screened, and full-text articles assessed for eligibility by two independent authors. Meta-analysis was performed using random-effects modelling with the DerSimonian and Laird method. RESULTS: We found 220 studies initially, which yielded 11 studies for inclusion in the qualitative review and 10 in the quantitative analysis - 5 studies on fibromyalgia, 3 on chronic fatigue syndrome and 3 on functional gastrointestinal disorder. Nine of the 11 studies found increased rates of JH in FSS compared to controls, though most studies were fair to poor in quality. Meta-analysis showed a weighted summary effect odds ratio of 3.27 (95% CI: 1.83, 5.84; p < 0.001) of JH in FSS, suggesting greater odds of FSS in individuals with JH than in those without. CONCLUSIONS: There is some evidence for an association between FSS and JH, but this is limited by the generally poor quality of studies and the narrow range of FSS studied. Better research is needed to confirm these findings as well as evaluate causation using prospective cohort studies.

Desvenlafaxine in the treatment of major depression: an updated overview.

Introduction: Major depressive disorder (MDD) remains one of the most prevalent mental health conditions. It is a chronic, relapsing condition and despite multiple treatment options, many patients fail to achieve remission of symptoms. Inadequacy of treatment has stimulated the search for agents with significant therapeutic advantages.Areas covered: This review examines literature concerning the use of desvenlafaxine in the treatment of MDD published since a previous analysis in this journal in 2014. Published papers were identified via a PubMed and Web of Science search and excluded congress presentations. Results from clinical trials in MDD, systematic reviews, and post hoc analyses in patient subgroups, are reviewed.Expert opinion: Desvenlafaxine was an effective antidepressant with favorable safety and tolerability in adults. Efficacy was demonstrated in the subgroup of peri- and post-menopausal women with MDD but not in children and adolescents. There is a relatively low potential for drug-drug interactions due to its metabolic profile. Hepatic impairment does not significantly alter dose requirements, whereas severe renal disease requires some adjustments of dose. Desvenlafaxine maybe suitable in patients with comorbid physical illnesses. Desvenlafaxine can be a first line consideration for the treatment of cases of MDD uncomplicated by medical comorbidities.

Dopamine D(1) receptor binding in the anterior cingulate cortex of patients with obsessive-compulsive disorder.

Functional neuroimaging studies in patients with obsessive-compulsive disorder (OCD) suggest there is a hyperactivation of the anterior cingulate cortex (ACC) during provocation of symptoms and conflict-inhibition tasks. Since dopamine, acting through D(1) receptors is suggested to modulate ACC activity, we hypothesised that there would be an altered D(1) binding potential (BP) in the ACC of OCD patients. Using [(11)C]-SCH23390 and positron emission tomography, we report significantly reduced D(1) BP in seven drug-free OCD patients compared with matched healthy controls. These findings suggest mesocortical dopamine inputs via D(1) receptors may play a role in the aetiology of OCD.

Trends in antipsychotic prescribing practices in an urban community mental health clinic.

OBJECTIVE: Availability of new psychotropic agents, and formulations, as well as expanded indications for previously available agents, has had an impact on prescribing patterns in community psychiatric practice. This study tracked changes in patient diagnostic profiles and compared antipsychotic prescribing patterns for patients managed by a continuing care team over a 2.25-year period. METHOD: Data pertaining to patient diagnoses and psychotropic medications was obtained from sequential cross-sectional file review and the pharmacy database. Data were collected in late 2004 (n = 224) and early 2007 (n = 294). RESULTS: The majority of patients suffered from DSM-IV schizophrenia, schizoaffective and related disorders (68% in 2004, 71% in 2007). Second generation antipsychotic (SGA) medications (79% in 2004, 99% in 2007 of all antipsychotics) were the most widely used agents. Use of quetiapine as a proportion of all oral SGAs increased (8% to 17%) as did that of long-acting risperidone (<1% to 17% of all antipsychotics) paralleled by a decline in long-acting first generation antipsychotic agents (15% to <1%). Significant changes in the prescription of non-benzodiazepine hypnotics and mood stabilizers were also noted. CONCLUSIONS: Statistically significant changes in prescribing patterns of antipsychotics during the study period were noted. Likely causes are discussed.

Treatment of cognitive dysfunction in chronic schizophrenia by augmentation of atypical antipsychotics with buspirone, a partial 5-HT(1A) receptor agonist.

OBJECTIVES: To assess effects of a semi-acute administration of buspirone in comparison to a placebo on cognitive function and negative symptoms in patients with schizophrenia and schizoaffective disorder. METHODS: In a 6-week, double-blind, placebo-controlled, independent groups study 18 subjects (14 males, four females) received in random order either placebo or buspirone (15-30 mg/day). A neuropsychological assessment using the Hopkins verbal learning test (HVLT) simple reaction time (SRT), choice reaction time (CRT), n-back spatial working memory task and the stroop colour and word test was performed at baseline and final visit. Symptom rating scales were administered at testing weeks 0, 2, 4 and 6. RESULTS: Repeated measures ANOVA was used to examine changes in performance on tests over time. There were no statistically significant differences between placebo and buspirone treatments on either cognitive function measures or symptom ratings. CONCLUSION: Semi-acute adjunct treatment with buspirone may be too short to be clinically efficacious in patients with schizophrenia. Intrinsic activation of 5-HT(1A) receptors by atypical antipsychotics may hinder the ability of buspirone to further improve cognitive functions. Buspirone did not affect clinical outcomes for this chronically ill group of patients being treated with atypical antipsychotic drugs.

Stability of cognitive impairment in chronic schizophrenia over brief and intermediate re-test intervals.

OBJECTIVE: This study examined between- and within-subject stability of cognitive performance in individuals with chronic schizophrenia. METHODS: Thirty individuals with schizophrenia and 20 healthy controls matched by age, sex, education, and estimated IQ underwent repeated cognitive assessments at baseline and 30 days using computerized tests of psychomotor function, visual attention/information processing, non-verbal learning, and executive function. RESULTS: Compared to healthy controls, individuals with schizophrenia scored lower on all cognitive measures and demonstrated greater variability in cognitive performance. Within-subject variability in cognitive performance in both the schizophrenia and healthy control groups remained stable at brief (i.e., hours) and intermediate (i.e., one month) assessments. CONCLUSIONS: These results demonstrate the stability of between- and within-subject variability in cognitive performance in schizophrenia, and suggest that variability in cognitive performance may reflect an inherent characteristic of the disorder, rather than differences in test-retest reliability/error of cognitive measures.

The impact of a changed environment on arousal levels of patients in a secure extended rehabilitation facility.

OBJECTIVE: This study sought to investigate the effect of changes of the physical ward environment on levels of arousal and aggression in long-stay patients in a secure extended rehabilitation facility. METHOD: Seclusion episodes, extended seclusion episodes, staff report of aggressive incidents and Brief Psychiatric Rating Scale (BPRS) measures of psychopathology were compared in the same group of long-stay rehabilitation patients over a period of 3 months before and 3 months after a move from a temporary, refurbished medical ward to a large, light-filled, purpose-built facility. RESULTS: Fifteen patients were present during both investigation periods. The majority were male (80%) and had a diagnosis of schizophrenia (53%) or schizoaffective disorder (13%). There were statistically significant reductions in the mean number of seclusion episodes, mean number of extended seclusion episodes (> 4 hours) and BPRS total score following the move. There were statistically significant increases in ambient light conditions in the new unit. CONCLUSIONS: The physical environment of long-stay rehabilitation wards may influence aggressive behaviour and arousal in chronically ill patients.

Agomelatine for depression: expanding the horizons?

INTRODUCTION: Agomelatine is an antidepressant with unique pharmacological actions; it is both a melatonin agonist and selective serotonin antagonist. Both actions combined are necessary for antidepressant efficacy. Effects on melatonin receptors enable resynchronisation of disrupted circadian rhythms with beneficial effects on sleep patterns. Areas covered: The issue of use of an antidepressant for depression co-morbid with somatic disorders is covered by the authors. A review of the literature from 2000 to August 2018 was undertaken using Scopus and Web of Science with the key words: agomelatine, depression, medical illness. Depression in Parkinson's disease, cardiovascular illness and type II diabetes is reviewed with evidence of efficacy. Bipolar depression and seasonal affective disorder may also react favourably. Agomelatine may have specific efficacy on symptoms of anhedonia. Expert opinion: Despite approval in some major jurisdictions, the drug has failed to gain registration in the United States. A defining issue may be questions about longer term efficacy: unequivocal effectiveness in placebo-controlled relapse prevention studies has not always been demonstrated. Continuation studies suggest maintenance of clinical responsiveness. A major disadvantage of the drug is its' potential hepatotoxicity and the need for repeated clinical laboratory tests.

Spatial working memory and problem solving in schizophrenia: the effect of symptom stabilization with atypical antipsychotic medication.

Reasoning and problem solving in the spatial domain are important aspects of executive function that are reliably impaired in schizophrenia, and the Groton Maze Learning Test(c) (GMLT) provides a valid measure of spatial working memory. In the current study, 34 patients with first-episode schizophrenia and 20 matched controls were assessed for baseline spatial working memory abilities using this hidden maze learning test. Approximately one month after baseline assessment, allowing for symptoms to stabilize in response to treatment with therapeutic doses of atypical antipsychotic medications for individuals with schizophrenia, all participants were again assessed with the GMLT. Prior to pharmacologic intervention, patients with schizophrenia showed significant impairments in performance of all aspects of the GMLT, including measures of learning efficiency and error monitoring. One month of treatment was associated with a reliable improvement in these domains, although impairments in accuracy and error monitoring on this spatial working memory test persisted despite symptomatic improvement. These results indicate that impairments in spatial working memory are present at the earliest stages of the illness, and that such deficits in performance remain present, albeit ameliorated, after treatment with atypical antipsychotic medication.

An investigation of the effect of immediate and extended release venlafaxine on nocturnal melatonin and cortisol release in healthy adult volunteers.

The secretion of the hormone melatonin is particularly robust to the effect of pharmacological agents. Medications may alter melatonin levels through either altering adrenergic activity or affecting liver enzymes involved in melatonin metabolism. The aim of this study was to investigate the effect of venlafaxine, a third generation antidepressant with known adrenergic properties on melatonin secretion. A further aim of the study was to investigate the correlation between plasma and salivary measures on this medication. Eight healthy adult participants (four males, four females) took part in this double blind placebo controlled randomised trial. Participants were tested on 3 nights after taking venlafaxine XR (75 mg), venlafaxine IR (75 mg) or placebo. Participants were placed in a darkened room between 1900 and 0300 h and regular temperature readings, blood and saliva samples were drawn to assess melatonin and cortisol secretion in each condition. There was no significant effect of venlafaxine IR or XR on melatonin concentrations in plasma or saliva and no effects on other circadian parameters including cortisol and temperature. It was notable that the correlation between plasma and salivary melatonin levels became poor after drug treatment. These results indicate that at low doses the mixed serotonergic and noradrenergic drug venlafaxine has no effect on nocturnal melatonin concentrations.