Subanesthetic ketamine infusion therapy can produce fast-acting antidepressant effects in patients with major depression. How single and repeated ketamine treatment modulates the whole-brain functional connectome to affect clinical outcomes remains uncharacterized.

Data-driven whole brain functional connectivity (FC) analysis was used to identify the functional connections modified by ketamine treatment in patients with major depressive disorder (MDD). MDD patients (N = 61, mean age = 38, 19 women) completed baseline resting-state (RS) functional magnetic resonance imaging and depression symptom scales. Of these patients, n = 48 and n = 51, completed the same assessments 24 h after receiving one and four 0.5 mg/kg intravenous ketamine infusions. Healthy controls (HC) (n = 40, 24 women) completed baseline assessments with no intervention. Analysis of RS FC addressed effects of diagnosis, time, and remitter status.

Significant differences (p < 0.05, corrected) in RS FC were observed between HC and MDD at baseline in the somatomotor network and between association and default mode networks. These disruptions in FC in MDD patients trended toward control patterns with ketamine treatment. Furthermore, following serial ketamine infusions, significant decreases in FC were observed between the cerebellum and salience network (SN) (p < 0.05, corrected). Patient remitters showed increased FC between the cerebellum and the striatum prior to treatment that decreased following treatment, whereas non-remitters showed the opposite pattern.

Results support that ketamine treatment leads to neurofunctional plasticity between distinct neural networks that are shown as disrupted in MDD patients. Cortico-striatal-cerebellar loops that encompass the SN could be a potential biomarker for ketamine treatment.

As the pathophysiology of Covid-19 emerges, this paper describes dysphagia as a sequela of the disease, including its diagnosis and management, hypothesised causes, symptomatology in relation to viral progression, and concurrent variables such as intubation, tracheostomy and delirium, at a tertiary UK hospital.

During the first wave of the Covid-19 pandemic, 208 out of 736 patients (28.9 per cent) admitted to our institution with SARS-CoV-2 were referred for swallow assessment. Of the 208 patients, 102 were admitted to the intensive treatment unit for mechanical ventilation support, of which 82 were tracheostomised. The majority of patients regained near normal swallow function prior to discharge, regardless of intubation duration or tracheostomy status.

Dysphagia is prevalent in patients admitted either to the intensive treatment unit or the ward with Covid-19 related respiratory issues. This paper describes the crucial role of intensive swallow rehabilitation to manage dysphagia associated with this disease, including therapeutic respiratory weaning for those with a tracheostomy.

To explore the phenomenology of auditory verbal hallucinations (AVHs) in a clinical sample of young people who have a ‘non-psychotic’ diagnosis.

Ten participants aged 17–31 years with presentation of emotionally unstable personality disorder or post-traumatic stress disorder and frequent AVHs were recruited and participated in a qualitative study exploring their subjective experience of hearing voices. Photo-elicitation and ethnographic diaries were used to stimulate discussion in an otherwise unstructured walking interview.

‘Non-psychotic’ voices comprised auditory qualities such as volume and clarity. Participants commonly personified their voices, viewing them as distinct characters with which they could interact and form relationships. There appeared to be an intimate and unstable relationship between participant and voice, whereby voices changed according to the participants’ mood, insecurities, distress and circumstance. Equally, participants reacted to provocation by the voice, leading to changes in mood and circumstance through emotional and physical disturbances. In contrast to our previous qualitative work in psychosis, voice hearing was not experienced with a sense of imposition or control.

This phenomenological research yielded in-depth and novel accounts of ‘non-psychotic’ voices which were intimately linked to emotional experience. In contrast to standard reports of voices in disorders such as schizophrenia, participants described a complex and bi-directional relationship with their voices. Many other features were in common with voice hearing in psychosis. Knowledge of the phenomenology of hallucinations in non-psychotic disorders has the potential to inform future more successful management strategies. This report gives preliminary evidence for future research.

Cocaine abuse continues to be epidemic, and yet there are no FDA approved medications for the treatment of cocaine use disorders. A previous pilot study conducted by this author suggested that quetiapine may help reduce the cravings for cocaine in 22 individuals with cocaine dependence.

This 12-week, prospective, intent-to-treat, double-blind, randomized, placebo-controlled study examined the effectiveness of quetiapine (Seroquel SR™) versus matched placebo for the treatment of cocaine dependence in non-psychotic individuals. Sixty individuals with a diagnosis of cocaine dependence were randomized in this study, 29 into the quetiapine arm, and 31 into the placebo arm. Those who were randomized to quetiapine were titrated up to a target dose of 400 mg/day of quetiapine, while those on the placebo arm were given a matched placebo. All subjects had weekly clinic visits for a cognitive-behavioral therapy group session. Outcome measures included questionnaires of cocaine use, cravings for cocaine, and urine drug screen.

Initial analyses indicate that the intensity, frequency, and length of cocaine cravings were reduced over 6 weeks in both the quetiapine and placebo groups. All hazard analyses indicated that the total money spent on cocaine also decreased in both groups, with a trend toward greater decrements in cocaine use the longer they remained in the study. Data analyses are ongoing to determine the potential effect of quetiapine on treatment of cocaine addiction.

Conclusions regarding the use of quetiapine as a treatment for cocaine dependence will be discussed.

As awareness of ADHD has increased throughout the world, interest has grown beyond the constellation of ADHD symptoms, including long-term effects and impact on people's lives.

To examine the consequences of childhood ADHD and the relevance of these outcomes in different world regions.

This analysis examined the publication trends of studies of long-term outcomes of ADHD over time and among world regions.

Study identification followed Cochrane guidelines. Twelve databases were searched for reports published in English 1980–2010. Limiting criteria were designed to maximize study inclusion while maintaining a high level of study rigor: the studies were to

1. (1) be peer-reviewed,

2. (2) be primary study reports,

3. (3) include a comparator group or baseline, and

4. (4) report outcome results measured for a mean of 8 years (prospective studies, range of all studies was 6 months-40 years) after the start of the study, in late adolescence, or adulthood.

The fully-defined electronic search yielded 4615 citations, which were then reviewed manually based on the titles and abstracts, yielding a final of 371 studies.

Study publication trends analysed included: publication year, country and world region of origin, outcome types, and study types. In general, the numbers of studies published per year globally has increased substantially (from 2 in 1980 to more than 40/year in 2007 and 2008) with differences observed between Europe and North America.

Analysis of publication trends can provide insight into outcomes of ADHD and the focus of specific world regions.

Supported by Shire Development Inc.

As awareness of ADHD has increased worldwide, interest has grown beyond the constellation of ADHD symptoms, to include long-term impact on people's lives and society in general.

Examine the results of studies of long-term life consequences of ADHD.

To identify areas of life affected long-term by ADHD and differences in outcomes with and without ADHD treatment.

Following Cochrane guidelines, 12 databases were searched for studies published in English (1980–2010). Limiting criteria maximized study inclusion while maintaining high study rigor: (1) peer-reviewed, (2) primary study reports, (3) including a comparator condition, and (4) reporting long-term outcomes (mean 8 years, range 6 months-40 years from study start for prospective studies; subjects in adolescence or adulthood for retrospective or cross-sectional studies). The fully-defined electronic search yielded 4615 citations. Manual review based on titles and abstracts yielded 340 studies included in this analysis of outcomes.

The majority of studies (86%, 243 of 281; studies of untreated ADHD only) showed that untreated ADHD has substantial negative long-term outcomes, encompassing nine broad-ranging areas of life: non-medicinal drug use/addictive behaviour, antisocial behaviour, academic achievement, occupational achievement, public services use, self-esteem, social function, obesity, and driving outcomes. In contrast, most studies including ADHD pharmacotherapy and/or non-pharmacotherapy (94%, 46 of 49) showed that compared with baseline or untreated ADHD, long-term outcomes improved or stabilized with treatment of ADHD.

ADHD has notable negative long-term consequences, and this negative impact may be reduced with treatment of ADHD. Supported by Shire Development Inc.

Numerous studies have applied novel multivariate statistical approaches to the analysis of brain alterations in patients with schizophrenia. However the diagnostic accuracy of the reported predictive models differs largely, making it difficult to evaluate the overall potential of these studies to inform clinical diagnosis.

We conducted a comprehensive literature search to identify all studies reporting performance of neuroimaging-based multivariate predictive models for the differentiation of patients with schizophrenia from healthy control subjects. The robustness of the results as well as the effect of potentially confounding continous variables (e.g. age, gender ratio, year of publication) was investigated.

The final sample consisted of n=37 studies studies including n=1491 patients with schizophrenia and n=1488 healthy controls. Metaanalysis of the complete sample showed a sensitivity of 80.7% (95%-CI: 77.0 to 83.9%) and a specificity of 80.2% (95%-CI: 83.3 to 76.7%). Separate analysis for the different imaging modalities showed similar diagnostic accuracy for the structural MRI studies (sensitivity 77.3%, specificity 78.7%), the fMRI studies (sensitivity 81.4%, specificity 82.4%) and resting-state fMRI studies (sensitivity 86.9%, specificity 80.3%). Moderator analysis showed significant effects of age of patients on sensitivity (p=0.021) and of positive-tonegative symptom ratio on specificity (p=0.028) indicating better diagnostic accuracy in older patients and patients with positive symptoms.

Our analysis indicate an overall sensitivity and overall specificity of around 80 % of neuroimaging-based predictive models for differentiating schizophrenic patients from healthy controls. The results underline the potential applicability of neuroimaging-based predictive models for the diagnosis of schizophrenia.

Animal research suggests that weight gain may be caused by olanzapine-induced melatonin suppression. We conducted a pilot study of psychiatric patients treated with olanzapine to examine if melatonin was suppressed and if so the dose needed to replace this deficit. The relationship between melatonin and metabolic indices was also examined.

Ten patients with schizophrenia (N=3), schizoaffective disorder (N=3), or bipolar disorder (N=4) completed the study. All patients were male, average age 50.6 years. Patients were treated with olanzapine for 5 weeks, then randomized to either 0.3mg (N=4) or 3mg (N=6) of melatonin supplementation in addition to the olanzapine for another 6 weeks. We obtained baseline, week-6, and week-12 measures of the major metabolite of melatonin in the urine, 6-Sulfatoxymelatonin (aMT6s) adjusted for creatinine excretion. We measures weekly weight, glycemia, cholesterol, and triglycerides.

Olanzapine treatment was associated with a trend toward decreases in melatonin from baseline to week-6 (p=.14). Analysis of a subsample of patients diagnosed with schizoaffective or bipolar disorder showed significant decreases from baseline to week-6 (p=.02). Both supplementation with melatonin by 0.3mg and 3mg increased urinary melatonin levels from week-6 to week-12 (p=.12 and p=.02 respectively). Total cholesterol increased initially but demonstrated a trend for decrease when melatonin was supplemented (p=.10).

Olanzapine appears to be related to melatonin suppression. Melatonin supplementation reverses this suppression and may have the potential to reverse metabolic effects associated with olanzapine. Further studies are needed to examine the metabolic effects of olanzapine with melatonin.

Cocaine abuse continues to be epidemic, and yet there are no FDA approved medications for the treatment of cocaine use disorders within the United States.

This 12-week, prospective, double-blind, randomized, placebo-controlled study examined the effectiveness of quetiapine (Seroquel XRTM) versus matched placebo for the treatment of cocaine dependence in non-psychotic individuals. Sixty Individuals with a diagnosis of cocaine dependence were randomized in this study. Those who were randomized to quetiapine (N=29) were titrated up to a target dose of 400 mg/day of quetiapine, while those in the placebo arm (N=31) were given a matched placebo. All subjects had weekly clinic visits and a cognitive-behavioral therapy group session. Outcome measures included questionnaires of cocaine use, money spent on cocaine, and urine drug screens (UDS).

The drop-out rate was substantial at 68%, however there were no group differences between the two arms of the study. Using a repeat measures ANCOVA, as a whole, the subjects in this study improved by reducing their self-reported use of cocaine (p=.018) and self reported money spent on cocaine (p=.041) over the course of the study. However, the quetiapine group was not significantly different from the placebo group. in addition, cox regression analyses yielded non-significant differences (p = .65) between groups in predicting sobriety, as defined as three weeks negative UDS.

This study did not find group differences between the quetiapine and placebo arms, indicating that quetiapine does not appear to be beneficial in the treatment of cocaine dependence.

Neurobiological models of auditory verbal hallucination (AVH) have been advanced by symptom capture functional magnetic resonance imaging (fMRI), where participants self-report hallucinations during scanning. To date, regions implicated are those involved with language, memory and emotion. However, previous studies focus on chronic schizophrenia, thus are limited by factors, such as medication use and illness duration. Studies also lack detailed phenomenological descriptions of AVHs. This study investigated the neural correlates of AVHs in patients with first episode psychosis (FEP) using symptom capture fMRI with a rich description of AVHs. We hypothesised that intrusive AVHs would be associated with dysfunctional salience network activity.

Sixteen FEP patients with frequent AVH completed four psychometrically validated tools to provide an objective measure of the nature of their AVHs. They then underwent fMRI symptom capture, utilising general linear models analysis to compare activity during AVH to the resting brain.

Symptom capture of AVH was achieved in nine patients who reported intrusive, malevolent and uncontrollable AVHs. Significant activity in the right insula and superior temporal gyrus (cluster size 141 mm3), and the left parahippocampal and lingual gyri (cluster size 121 mm3), P < 0.05 FDR corrected, were recorded during the experience of AVHs.

These results suggest salience network dysfunction (in the right insula) together with memory and language processing area activation in intrusive, malevolent AVHs in FEP. This finding concurs with others from chronic schizophrenia, suggesting these processes are intrinsic to psychosis itself and not related to length of illness or prolonged exposure to antipsychotic medication.

The authors have not supplied their declaration of competing interest.