With a growing number of elderly persons, geriatric depression - associated with important morbidity and mortality- is becoming a significant health problem. Given the risk of polypharmacy and increased side effects, alternative non pharmaceutical treatments such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) may be solution. Recently, the FDA approved deep brain TMS (dTMS) for depression, not only stimulating deeper cortical areas but response and remission rates may be better, especially in elderly populations. Nevertheless, beneficial follow-up options following rTMS treatment remains to be determined. Therefore, one week after the last accelerated dTMS, all patients followed a 3 week open label tDCS with a home-use device. Study rationale and preliminary findings will be discussed.

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Late life depression is a major global health issue, with an estimated 7% of older adults suffering from this mental disorder. Depression is one of the most important predictors for suicide in the elderly. However, it is often difficult to recognize and manage, making treatment-resistance a common occurrence. Treatment-resistant depression itself is also a known risk factor for suicide. Recently, non-invasive neuromodulation techniques have been used as a new treatment for depression and suicidality with promising results.

This study aims to investigate the effect of adTMS (accelerated deep Transcranial Magnetic Stimulation) and tDCS (transcranial Direct Current Stimulation) on the suicidality of elderly, therapy-resistant depressed patients. The hypothesis is that suicidal ideation and risk of suicide will decrease after a treatment with adTMS and tDCS.

In this randomized double-blinded sham-controlled clinical trial, geriatric therapy-resistant depressive patients will receive adTMS treatment (See: Figure 1). Suicidality will be assessed before and after the active or sham treatment, through the Columbia Suicide Severity Rating Scale (C-SSRS) and Beck Scale for Suicide Ideation (BSI). After one week of rest, all patients will receive an at-home tDCS treatment for 3 weeks. Likewise, the suicide risk will be estimated before and after the tDCS. During the screening period, the severity of the patients’ depressive symptoms will be determined by using the 17-item Hamilton Depression Rating Scale (HDRS-17). In total, the trial will last for 5 weeks, and suicidality will be examined at five different time points (during screening, at T0, T1, T2 and T3).

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Compulsory admission procedures of patients with mental disorders vary between countries in Europe. The Ethics Committee of the European Psychiatric Association (EPA) launched a survey on involuntary admission procedures of patients with mental disorders in 40 countries to gather information from all National Psychiatric Associations that are members of the EPA to develop recommendations for improving involuntary admission processes and promote voluntary care.

The survey focused on legislation of involuntary admissions and key actors involved in the admission procedure as well as most common reasons for involuntary admissions.

We analyzed the survey categorical data in themes, which highlight that both medical and legal actors are involved in involuntary admission procedures.

We conclude that legal reasons for compulsory admission should be reworded in order to remove stigmatization of the patient, that raising awareness about involuntary admission procedures and patient rights with both patients and family advocacy groups is paramount, that communication about procedures should be widely available in lay-language for the general population, and that training sessions and guidance should be available for legal and medical practitioners. Finally, people working in the field need to be constantly aware about the ethical challenges surrounding compulsory admissions.

Although the subgenual anterior cingulate cortex (Cg25: Brodmann area 25) is an important target area in the treatment of affective disorders, its involvement in the evaluation of emotional salience of visual stimuli during depressed episodes is not quite understood. Research regarding the neurocircuitry in mood disorders suggests an important role of this anatomical region for affective information processing.

In this study, we focused on Cg25 neuronal responses in depressed females using a paradigm in which emotions are elicited without explicit cognitive control, relying on the salient nature of the mood inducing stimuli eliciting approach-related emotions (like happiness) or withdrawal-related emotions (like disgust).

Twelve treatment-resistant melancholic depressed women and 12 age-matched healthy female control subjects were asked to passively view blocks of baby faces when undergoing functional magnetic resonance imaging (fMRI).

Compared to the healthy females, the depressed patients displayed significantly higher bilateral Cg25 neuronal activities in both emotional experiences. Whereas in melancholically depressed women, right-sided Cg25 activity was comparable for both emotional experiences, we found significantly less leftsided Cg25 neuronal activity during the withdrawal-related emotional experience.

Our results could indicate that in depressed women the left Cg25 modulates intense visceral emotional responses to aversive visual stimuli. Our observations could help to explain why in unipolar melancholic depression the left Cg25 provides a valid target region for antidepressant treatment strategies, such as deep brain stimulation and anterior cingulotomy and nervus vagus stimulation therapy, which all seem to correlate with decreases in left Cg25 activity.

Major depression is one of the most common mental diseases, and quite a number of patients are resistant to several psychopharmacological interventions, even when applying current treatment guidelines. To date, it remains unclear as to how the serotonergic system is implicated in treatment-resistance found in melancholically depressed patients.

In this study, we examined the involvement of post-synaptic 5-HT2A receptors in the pathophysiology of treatment resistance in major depression with 123I-5-I-R91150 SPECT, focusing on the frontal cortex and hippocampus.

15 unipolar antidepressant naïve (ADN) patients and 15 treatment-resistant depressed (TRD) patients, all of the melancholic subtype, matched for age and gender were studied. All subjects were antidepressant free when they underwent a static 123I-5-I-R91150 SPECT scan.

Compared to ADN patients, TRD patients displayed significantly less 5-HT2A receptor binding index (BI) in the dorsal regions of the prefrontal cortex and in the anterior cingulate cortex. No hippocampal 5-HT2A receptor BI differences were observed.

Our results suggest that when confronted with treatment resistance in melancholic depression the 5-HT2A receptors in the DPFC-ACC axis are significantly more down-regulated when compared to depressed ADN patients. This might to some extent explain the observed continued cognitive problems and might reflect the long-term serotonin depletion with reduced neurogenesis in treatment resistant patients.

Although repetitive Transcranial Magnetic Stimulation (rTMS) is frequently used to examine emotional changes in healthy volunteers, it remains largely unknown how rTMS is able to influence emotion.

In this sham-controlled single-blind crossover study using fMRI, we examined in 20 right-handed healthy female volunteers whether a single high frequency (HF)-rTMS session applied to the left dorsolateral prefrontal cortex (DLPFC) could influence emotional processing while focussing on blocks of positively and negatively valenced baby faces. The task instruction was to focus on one's own emotional status elicited by the visual stimuli.

A single HF-rTMS session selectively influenced the processing of positively and negatively valenced baby faces. When positive information was being processed, one active left-sided HF-rTMS session resulted in enhanced neuronal activity in the left superior frontal cortex (Brodmann area 10) and right inferior parietal cortex (Brodmann area 39). When negative information was processed, one active stimulation session attenuated neuronal activity in the right insula, while sham stimulation did not.

These observations suggest that after one active HF-rTMS session, psychophysiological reactions while processing withdrawal-related stimuli decrease. The increased neuronal activity while processing of positively valenced baby faces might reflect enhanced task-related processing caused by the neuronal activation of the left DLPFC, which could indicate that females are more able to empathize with the depicted happy baby faces. Our results add further evidence as to why HF-rTMS applied to the left DLPFC might improve mood in depressive populations.

Current evidence suggests that high frequency repetitive Transcranial Magnetic Stimulation (HF-rTMS) of the left dorsolateral prefrontal cortex (DLPFC) might be a promising treatment strategy for depression. However, due to rather modest clinical results, the efficacy of rTMS in depressed patients is still under debate. As melancholic depression seems to affect psychomotor activity, in this study, we wanted to evaluate whether HF-rTMS treatment affects psychomotor activity. We also wanted to examine whether the severity of psychomotor retardation could predict clinical outcome.

Our group consisted of twenty antidepressant-free unipolar depressed patients of the melancholic subtype. All were considered at least stage II treatment resistant. Depression severity was assessed with the Hamilton Depression Rating Scale (HDRS) and psychomotor symptoms with the Depressive Retardation Rating Scale (DRRS). All received 10 sessions of HF-rTMS delivered on the left DLPFC.

Forty percent of the patients showed a reduction of at least 50% on their initial HDRS score and were defined as HF-rTMS responders.

The severity of psychomotor retardation, as measured with the DDRS, did not predict clinical outcome. HF-rTMS treatment resulted in significant decreases in DDRS scores for responders as well as for non-responders. However: the better the clinical outcome, the higher the observed level of psychomotor improvement.

Our results suggest that HF-rTMS might act on the ‘psychomotor’ level and this might add some further information as to why this kind of treatment can be beneficial for severely depressed patients of the melancholic subtype.

Repetitive transcranial magnetic stimulation (rTMS) on the left dorsolateral prefrontal cortex (DLPFC) is safe and efficient for treatment-resistant depression (TRD). More intensive rTMS protocols could improve clinical outcome.

We report on an intensive high frequency (HF)-rTMS treatment protocol in patients unresponsive to current treatment strategies.

Monitoring effectiveness and tolerability.

Patients were diagnosed with TRD, schizoaffective disorder, bipolar type or bipolar type I disorder, mixed episode. All were unresponsive to adequate therapy (rTMS excluded).HF-rTMS was administrated on the left DLPFC under MRI guidance. In each 20 Hz stimulation session, the patient received 40 trains of 1.9 seconds duration at 120% of the motor threshold. The 20 HF-rTMS sessions were spread over 4 days (5 times/day), yielding a total of 31,200 stimuli.

There were neither seizures nor important adverse events. The bipolar patient clinically responded (Hamilton Depression Rating Scale (HAMD) from 20 to 9) following treatment day 1. After completing the protocol a week earlier, the TRD patient's HAMD went from 28 to 5. There was a 5 point decrease in the score of the schizoaffective patient. He improved on the brief psychiatric rating subscales blunted affect and emotional withdrawal. No positive symptoms occurred. None of the patients had significant elevations in YMRS scores or in psychomotor activity.

‘Intensively’ targeting the left DLPFC was tolerated and safe. Our results suggest a strategy of HF-rTMS protocols in non-responders to classical treatment. Larger sham-controlled HF-rTMS studies should substantiate these recent findings.

The underlying physiological mechanisms as to why repetitive transcranial magnetic stimulation (rTMS) can treat depressed patients remains unclear and no clear biological markers are available to indicate a positive outcome for a given patient. Some data suggest that rTMS can influence hypothalamic-pituitary-adrenal (HPA) processes. In this study, we wanted to evaluate whether one session of high frequency (HF)-rTMS applied on the left dorsolateral prefrontal cortex (DLPFC) can predict a successful treatment outcome in a sample of antidepressant free unipolar depressed patients of the melancholic subtype.

Twenty one right-handed treatment resistant depressed patients were studied. Fifty two percent of the patients were considered as treatment responders, as defined by a 50% reduction in her/his baseline 17-item Hamilton Depression Rating Scale (HDRS) score. To examine acute HF-rTMS effects on the HPA- axis, we analyzed salivary cortisol levels, using a sham-controlled, ‘single’ blind, crossover design. Areas under the curves (AUC) were calculated for both real and sham HF-rTMS.

Real HF-rTMS resulted in salivary cortisol decreases, however only in HF-rTMS non-responders. No HF-rTMS influences were found in the responder group. Sham stimulation did not affect the HPA-axis. Non-responders were found to display a higher level of co-morbid personality disorders.

Our results may provide more insight into the underlying working mechanisms of HF-rTMS and could add further information about endocrinological functioning in affective disorders. Furthermore, personality features in combination with a ‘super-sensitive’ HPA system could be of importance to predict clinical outcome.

Repetitive transcranial magnetic stimulation (rTMS) affects neuronal circuits and neurotransmitter systems in the brain. Recent data suggest that this application could diminish ‘craving’ in patients with alcohol dependence.

Given these preliminary data, we examined whether one high frequency (HF)- rTMS session over the right dorsolateral prefrontal cortex (DLPFC) would reduce alcohol craving in alcohol dependent patients in their natural habitat.

After detoxification during hospitalization, 22 current alcohol dependent inpatients were included (8 female, 14 male; age = 49.95 ± 8.82y).

We used a sham-controlled between-subjects design where after randomization patients received under MRI guidance one right-sided DLPFC active HF-rTMS session or sham. In each high-frequency (20 Hz) stimulation session, patients received 1560 pulses at 110 % MT. The obsessive-compulsive drinking scale (OCDS) was collected at baseline, just before and just after the stimulation session on Friday after detoxification and on the three consecutive days following stimulation in patient's natural habitat.

Although the OCDS total score significantly decreased after the detoxification period, one sham-controlled stimulation session did not affect immediate craving measurements. Furthermore, no significant group differences were observed on OCDS total scores when patients were in their natural habitat.

Although the right DLPFC was targeted under MRI guidance, our preliminary results indicate that one sham-controlled HF-rTMS session does not affect craving in recently detoxified alcohol dependent patients. Besides the limited number of patients it could be possible that only one stimulation session could be insufficient to have a subjective effect on craving.

Suicidal behaviour is the consequence of the interaction between stressors and a diathesis or vulnerability. Evidence is accumulating that changes in the central nervous system contribute to this vulnerability. A substantial number of imaging studies in suicide attempters have been published, but most studies are characterized by small sample sizes and increased risk of false positive findings. Therefore, the current study aimed at a systematic review and meta-analysis of published study in order to describe consistently identified disturbances in brain structure and, or, functions.

Systematic review and meta-analysis of imaging studies of attempted suicide patients, affective controls and healthy volunteers, including structural and functional MRI studies and molecular imaging studies.

A reduced prefrontal perfusion or metabolism, a blunted increase in activation when challenged, and impairment of the prefrontal serotonergic system in association with a history of suicide attempts is shown in molecular imaging studies. Recent structural and functional imaging studies show changes in cortical and subcortical areas and their connections. Meta-analyses revealed structural deficits and functional changes in association with a history of suicidal behaviour. Structural findings included reduced volumes of the rectal gyrus, superior temporal gyrus and caudate nucleus. Functional differences between study groups included an increased reactivity of the anterior and posterior cingulate cortices to negatively valenced emotional stimuli. A number of methodological issues hamper the interpretation of findings. Nevertheless, there is increasing evidence of the involvement of a serotonin-mediated network in suicidal behaviour. The involvement of this network in decision-making, and particularly the prediction of reward and punshment, has been shown previously in healthy individuals.

A diathesis to suicidal behaviour appears to be associated with changes in biochemical, functional and structural brain characteristics, which point at the involvement of a serotonin-mediated decision-making network in the development of suicidal behaviour.

Obsessive-compulsive disorder (OCD) is a frequently reported comorbid disorder (20–30%) in patients with anorexia nervosa (AN). Increasing evidence suggests that repetitive transcranial magnetic stimulation (r-TMS) may be effective in the treatment of refractory OCD and to a lesser extent in AN. Hereby, different target areas: supplemental motor area (SMA) and orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex in AN. We report two patients with enduring AN and comorbid treatment resistant OCD treated with r-TMS.

Both female patients (34 and 26 years respectively) were hospitalized at the Eating Disorder Unit at the Ghent University Hospital. Treatment responses were evaluated with Yale Brown Obsessive Compulsive Scale (Y-BOCS) and weight gain. Inhibitory continuous thetaburst stimulation (cTBS) of the SMA followed by cTBS of the OFC was conducted during 20 sessions, 5 sessions a week, during 4 weeks. Stimulation intensity was respectively 100% and 80% of the motor treshold.

After cTBS treatment Y-BOCS score of both patients decreased (31 to 24 and 31 to 23 respectively). Only one patient showed a 10% increase of weight. The treatment was well tolerated. No significant side effects were reported.

Treatment resistant comorbid OCD in patients with AN may be succesfully treated with cTBS.

The authors have not supplied their declaration of competing interest.

Evidence suggests that repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) might be a promising new treatment procedure for depression. However, underlying working mechanisms of this technique are yet unclear. Multiple sessions of rTMS may – apart from the reported antidepressant effects – cause primary improvements in attentional control over emotional information, modulated by changes in cortical brain excitability within stimulated prefrontal regions.

In two experiments, we examined the temporary effects of high-frequency (HF) rTMS (10 Hz) applied over the left and right DLPFC on the attentional processing of emotional information and self-reported mood within samples of healthy volunteers.

The present study showed that one session of HF-rTMS over the right DLPFC produces instant impairments in the ability to inhibit negative information, in line with a characteristic cognitive vulnerability found in depressive pathology, whereas HF-rTMS of the left DLPFC did not lead to significant changes in attentional control. These effects could not be attributed to mood changes.

The findings of the present study may suggest a specific involvement of the right DLPFC in the attentional processing of emotional information.