Major depressive disorder (MDD) is a leading cause of morbidity and mortality. Shortfalls in treatment quantity and quality are well-established, but the specific gaps in pharmacotherapy and psychotherapy are poorly understood. This paper analyzes the gap in treatment coverage for MDD and identifies critical bottlenecks.

Seventeen surveys were conducted across 15 countries by the World Health Organization-World Mental Health Surveys Initiative. Of 35 012 respondents, 3341 met DSM-IV criteria for 12-month MDD. The following components of effective treatment coverage were analyzed: (a) any mental health service utilization; (b) adequate pharmacotherapy; (c) adequate psychotherapy; and (d) adequate severity-specific combination of both.

MDD prevalence was 4.8% (s.e., 0.2). A total of 41.8% (s.e., 1.1) received any mental health services, 23.2% (s.e., 1.5) of which was deemed effective. This 90% gap in effective treatment is due to lack of utilization (58%) and inadequate quality or adherence (32%). Critical bottlenecks are underutilization of psychotherapy (26 percentage-points reduction in coverage), underutilization of psychopharmacology (13-point reduction), inadequate physician monitoring (13-point reduction), and inadequate drug-type (10-point reduction). High-income countries double low-income countries in any mental health service utilization, adequate pharmacotherapy, adequate psychotherapy, and adequate combination of both. Severe cases are more likely than mild-moderate cases to receive either adequate pharmacotherapy or psychotherapy, but less likely to receive an adequate combination.

Decision-makers need to increase the utilization and quality of pharmacotherapy and psychotherapy. Innovations such as telehealth for training and supervision plus non-specialist or community resources to deliver pharmacotherapy and psychotherapy could address these bottlenecks.

Relationships between performance on various tests of executive functions and positive symptoms, especially delusions and hallucinations, have not been found consistently. This may be related to method of rating symptoms, to possible interactions between them, as well as to the low specificity of the cognitive test measures used. In this study, we have investigated the relationships between different aspects of positive symptomatology and several executive subprocesses.

Stable schizophrenia patients (n=96) were assessed for disorganization, delusion and hallucination symptoms rated from the Scale for Assessment of Positive Symptoms and the Scale for Assessment of Negative Symptoms. Interference sensitivity, inhibition and flexibility were assessed using the Wickens paradigm. The relationships between symptom dimensions as well as with cognitive and other potentially confounding variables were assessed using Pearson correlations and (simple and partial) stepwise regressions.

Generally consistent with the cognitive constructs used to account for positive symptoms, the results indicated relationships between delusions, disorganization and inhibition, and between hallucinations and interference sensitivity. However, these relationships appeared more complex than expected, with some being dependent on interactions between symptoms.

These results suggest: (i) that the global measures usually employed may not be appropriate for demonstrating specific relationships between symptoms and executive functions and (ii) that it is necessary to take into account the interactions between positive symptoms as well as with other factors to reveal these relationships.

DSM-IV cites <85% of expected body weight (EBW) as a guideline for the diagnosis of anorexia nervosa (AN) but does not require a specific method for calculating EBW. The purpose of the present study was to determine the degree to which weight cut-off calculations vary across studies, and to evaluate whether differential cut-offs lead to discrepancies in the prevalence of individuals who are eligible for the AN diagnosis.

Two coders independently recorded the EBW calculation methods from 99 studies that either (a) compared individuals with AN to those with subclinical eating disorders or (b) conducted AN treatment trials. Each weight cut-off was applied to a nationally representative (n=12001) and treatment-seeking (n=189) sample to determine the impact of EBW calculation on the proportion who met the AN weight criterion.

Coders identified 10 different EBW methods, each of which produced different weight cut-offs for the diagnosis of AN. Although only 0.23% of the national sample met the lowest cut-off, this number increased 43-fold to 10.10% under the highest cut-off. Similarly, only 48.1% of treatment seekers met the lowest cut-off, whereas 89.4% met the highest.

There is considerable variance across studies in the determination of the AN weight cut-off. Discrepancies substantially affect the proportion of individuals who are eligible for diagnosis, treatment and insurance reimbursement. However, differences may not be fully appreciated because the ubiquitous citation of the 85% criterion creates a sense of false consensus.

Poisoning with weak analgesics is a major public health problem because of easy accessibility of the compounds; however, few studies have investigated their influence on subsequent suicide in the context of subjects' psychiatric status and other factors.

This nested case-control study was based on the entire Danish population including all 21 169 suicide cases and 423 128 matched population controls. Data on hospital admissions for poisoning and confounding factors were retrieved from national medical and administrative registries. Conditional logistic regression was used to compute relative risk.

A prior hospital admission for poisoning with weak non-opioid analgesics significantly increased the risk of subsequent suicide [crude incidence rate ratio (IRR) 24.7, 95% confidence interval (CI) 22.1–27.6], and the effect of paracetamol poisoning was substantially stronger than that of poisoning with salicylates or non-steriodal anti-inflammatory drugs (NSAIDs). This association could not be explained by confounding from socio-economic or psychiatric factors. The elevated risk was extremely high during the first week following the overdose (adjusted IRR 738.9, 95% CI 173.9–3139.1), then declined over time but still remained significantly high 3 years later (adjusted IRR 4.2, 95% CI 3.5–5.0). Moreover, a history of weak analgesic poisoning significantly interacted with a person's psychiatric history, increasing the risk for subsequent suicide substantially more for persons with no history of psychiatric hospitalization than did it for those with such a history.

A history of non-fatal poisoning with weak analgesics is a strong predictor for subsequent suicide. These results emphasize the importance of intensive psychiatric care of patients following overdose.

Cognitive deficits in schizophrenia are well established and are known to be present during the first episode of a psychotic disorder. In addition, consistent heterogeneity within these impairments remains unexplained. One potential source of variability may be the level of pre-morbid adjustment prior to the onset of first-episode psychosis (FEP).

Ninety-four FEP patients and 32 healthy controls were assessed at baseline on several neuropsychological tests comprising six cognitive domains (verbal memory, visual memory, working memory, processing speed, reasoning/problem-solving and attention) and an abbreviated version of the full IQ. A global neurocognitive domain was also computed. Pre-morbid adjustment patterns were divided into three distinct groups: stable-poor, stable-good and deteriorating course.

Based on a cut-off of 0.8 for effect size, the stable-poor pre-morbid adjustment group was significantly more impaired on most cognitive domains and full IQ compared to the deteriorating group, who were more severely impaired on all measures compared to the stable-good group. The type of cognitive deficit within each subgroup did not differ and the results indicate that a global neurocognition measure may reliably reflect the severity of cognitive impairment within each subgroup.

Pre-morbid adjustment patterns prior to onset of psychosis are associated with severity but not type of cognitive impairment. Patients in the stable-poor group are generally more impaired compared to the deteriorating group, who are, in turn, more impaired than the stable-good group.

Depressed patients are biased in their response to negative information. They have been found to show a maladaptive behavioral and aberrant electrophysiological response to negative feedback. The aim of this study was to investigate the behavioral and electrophysiological response to feedback validity in drug-free depressed patients.

Fifteen drug-free in-patients with unipolar major depression disorder (MDD) and 30 demographically matched controls performed a time-estimation task in which they received valid and invalid (i.e. related and unrelated to performance) positive and negative feedback. The number of behavioral adjustments to the feedback and the feedback-related negativity (FRN) were measured.

Patients made fewer correct adjustments after valid negative feedback than controls, and their FRNs were larger. Neither patients nor controls adjusted their time estimates following invalid negative feedback.

The FRN results suggest that depressed drug-free in-patients have an atypical rostral anterior cingulate response to feedback that is independent of feedback validity. Their behavioral response to invalid negative feedback, however, is not impaired. This study confirms the notion that the behavioral responses of depressed individuals to negative feedback are context dependent.

Pain is a common symptom of chronic fatigue syndrome (CFS). We investigated the effects of the treatments used in the PACE trial [cognitive behavioural therapy (CBT), graded exercise therapy (GET), adaptive pacing therapy (APT) and specialist medical care (SMC)] on pain in CFS.

We compared pain outcomes including individual painful symptoms, taken from the CDC criteria for CFS and co-morbid fibromyalgia. We modelled outcomes adjusting for baseline variables with multiple linear regression.

Significantly less frequent muscle pain was reported by patients following treatment with CBT compared to SMC (mean difference = 0.38 unit change in frequency, p = 0.02), GET versus SMC (0.42, p = 0.01) and GET versus APT (0.37, p = 0.01). Significantly less joint pain was reported following CBT versus APT (0.35, p = 0.02) and GET versus APT (0.36, p = 0.02). Co-morbid fibromyalgia was less frequent following GET versus SMC (0.03, p = 0.03). The effect sizes of these differences varied between 0.25 and 0.31 for muscle pain and 0.24 and 0.26 for joint pain. Treatment effects on pain were independent of ‘change in fatigue’.

CBT and GET were more effective in reducing the frequency of both muscle and joint pain than APT and SMC. When compared to SMC, GET also reduced the frequency of co-morbid fibromyalgia; the size of this effect on pain was small.

Preliminary studies report no negative and a possible positive impact of deep brain stimulation (DBS) on cognition of patients with treatment-resistant depression (TRD). However, these studies neither controlled for practice effects nor compared active with sham stimulation.

To address these limitations, we compared 25 TRD patients, who underwent DBS of the ventral anterior limb of the internal capsule (vALIC), with 21 healthy controls (HCs) matched on gender, age and education level. Both groups did subtests of the Cambridge Neuropsychological Test Automated Battery assessing verbal and visuospatial memory, attention, cognitive flexibility, psychomotor functioning, planning and object naming. TRD patients were tested 3 weeks prior to DBS surgery (baseline), 3 weeks following surgery (T1) and following 52 weeks of DBS optimization (T2). HCs were tested at baseline, 6 weeks following baseline (T1) and 20–24 weeks following baseline (T2). Subsequently, TRD patients entered a randomized, double-blind crossover phase, in which they were tested in an active and a sham stimulation phase.

TRD patients did not improve on a test of immediate verbal recognition from baseline to T1, whereas HCs did (group x time: p = 0.001). Both TRD patients and HCs improved over sessions on tests measuring delayed verbal recall, visuospatial memory, planning and object naming (all p < 0.01). Active and sham stimulation did not have an impact on any of the tests differentially.

vALIC DBS neither has a lasting positive nor negative impact on cognition in TRD patients. DBS surgery might have a temporary negative effect on verbal memory.

To test the vascular depression hypothesis in the general population, we analyzed the association between current depression, medical history of depression, cognitive and somatic depressive symptom dimensions and measures of atherosclerosis [intima–media thickness (IMT) and carotid plaques].

We included a representative sample of 5000 participants from the Gutenberg Health Study (GHS). Depression was assessed by the nine-item Patient Health Questionnaire (PHQ-9), and IMT and carotid plaques were measured at both common carotid arteries using an edge detection system. Regression analyses were performed separately for participants with and without cardiovascular disease, adjusting for medical history, cardiovascular risk factors and psychotropic medication.

Contrary to hypotheses, we found no increased IMT for somatic symptoms of depression; the same was true for depression and cognitive symptoms in the fully adjusted model. Only a moderate relationship between medical history of depression and the presence of atherosclerotic plaques was maintained after correction.

The relationship between depression and atherosclerosis may be more complex than previously assumed. Although the vascular depression hypothesis was not supported, our results support the hypothesis that lasting depression leads to arteriosclerosis.

Limbic-cortical imbalance is an established model for the neurobiology of major depressive disorder (MDD), but imaging genetics studies have been contradicting regarding potential risk and resilience mechanisms. Here, we re-assessed previously reported limbic-cortical alterations between MDD relatives and controls in combination with a newly acquired sample of MDD patients and controls, to disentangle pathology, risk, and resilience.

We analyzed functional magnetic resonance imaging data and negative affectivity (NA) of MDD patients (n = 48), unaffected first-degree relatives of MDD patients (n = 49) and controls (n = 109) who performed a faces matching task. Brain response and task-dependent amygdala functional connectivity (FC) were compared between groups and assessed for associations with NA.

Groups did not differ in task-related brain activation but activation in the superior frontal gyrus (SFG) was inversely correlated with NA in patients and controls. Pathology was associated with task-independent decreases of amygdala FC with regions of the default mode network (DMN) and decreased amygdala FC with the medial frontal gyrus during faces matching, potentially reflecting a task-independent DMN predominance and a limbic-cortical disintegration during faces processing in MDD. Risk was associated with task-independent decreases of amygdala-FC with fronto-parietal regions and reduced faces-associated amygdala-fusiform gyrus FC. Resilience corresponded to task-independent increases in amygdala FC with the perigenual anterior cingulate cortex (pgACC) and increased FC between amygdala, pgACC, and SFG during faces matching.

Our results encourage a refinement of the limbic-cortical imbalance model of depression. The validity of proposed risk and resilience markers needs to be tested in prospective studies. Further limitations are discussed.