There is limited experimentally controlled neuroimaging research available that could explain how dissociative states occur and which neurobiological changes are involved in acute post-traumatic dissociation.

To test the causal hypothesis that acute dissociation is triggered bottom-up by a selective noradrenergic-mediated increase in amygdala activation during the processing of autobiographical trauma memories.

Women with post-traumatic stress disorder (n = 47) and a history of interpersonal childhood trauma underwent a within-participant, placebo-controlled pharmacological challenge paradigm (4.0 mg reboxetine versus placebo) employing script-driven imagery (traumatic versus neutral autobiographical memory recall). Script-elicited brain activation patterns (measured via functional magnetic resonance imagery) were analysed by means of whole-brain analyses and a pre-registered region of interest (i.e. amygdala).

Self-reported acute dissociation increased significantly during trauma (versus neutral) recall but did not differ between pharmacological conditions. The pharmacological manipulation was also unsuccessful in eliciting increased amygdala activation following script-driven imagery in the reboxetine (versus placebo) condition. In the reboxetine condition, trauma retrieval resulted in similar activation patterns as in the placebo condition (e.g. elevated brain activation in the middle occipital gyrus and supramarginal gyrus), albeit with different peaks.

Current (null) findings cast doubt on the suggested role of the amygdala in subserving dissociative processing of trauma memories. Alternative pharmacological manipulation approaches (e.g. ketamine) and analysis techniques (e.g. event-related independent component analysis) might provide better insight into the spatiotemporal dynamics and network shifts involved in dissociative experiences and autobiographical trauma memory recall.

Only three population-based observational human studies provided evidence that benzodiazepines (BZD) are associated with clinically adverse respiratory outcome. Striking was the finding that BZD drug exposure was associated with a 32% significantly increased adjusted risk of all-cause mortality, including, of note, the subgroup of individuals with no comorbidities. Causation, however, cannot be inferred in observational study design and, highly likely, recipients received BZD’s in these studies to help treating anxiety related to inter alia pre-existing respiratory symptoms.

Based on one fatal particular case, authors of current rapport explain what can go wrong when BZD’s are given in patient with respiratory impairment.

Authors provide a model on how an increase in carbon dioxide can lead to impaired cerebral autoregulation in a person with pre-existing respiratory decompensation. Discussion of integrative metabolic and vascular physiology.

Case rapport of a 18 y.o. otherwise healthy man, who was hospitalized with a novel episode of diabetic ketoacidosis accompanied by profound hypocapnia and anxiety, and who deteriorated and died shortly after airway management because of a clinically important acid-base balance disturbance caused by increased carbon dioxide. All the blood tests and results of respiratory monitoring were collected and carefully assessed.

Current case suggests that the P(CO(2))--HCO(3) hypothesis is consistent with known data on impaired cerebral autoregulation in diabetic ketoacidosis, driven mainly by increased levels of pCO2. In our opinion, it indicates the recommendation not to administrate BZD’s in patients with pre-existing compensatory hyperventilation as it may counter to the logic of adaptive physiology.

No significant relationships.

Antidepressant-induced galactorrhea and increases in prolactin levels have been sporadically reported among SSRI-related side effects.

Current rapport presents a case of 39 y.o. female who developed several adverse effects on paroxetine - including galactorrhoea - which improved on discontinuation of the drug.

Case discussion of 39-year old woman who was treated with paroxetine for her panic disorder and developed galactorrhoea with hyperprolactinemia that resolved upon discontinuation of the drug. Additionally, authors performed the literature search using PubMed and Embase to review the similar cases and used PDSP Database to assess the latest pharmacodynamic (PD) properties of paroxetine and other SSRI’s.

Literature review (1966–2020) revealed 24 prior published case reports of SSRI-induced galactorrhea in users of paroxetine (n=4), escitalopram (n=4), sertraline (n=2), citalopram (n=2), fluoxetine (n=3), fluvoxamine (n=2) and other non-assessable reports (n=7). Elevated prolactin levels were mostly observed with paroxetine and escitalopram and rarely with fluoxetine, fluvoxamine and sertraline. PD-assessment showed the highest binding affinity of paroxetine and escitalopram to SERT (kPi = 0.07-0.2 and 0.8-1.1 nmol/L respectively) compared to other SSRI’s, in absence of other relevant PD-properties

Increasing body of evidence shows that galactorrhea does occur among paroxetine female users. Pharmacodynamic mechanism of action is poorly understood but given the modern insights in relationship in serotonin and dopamine circuits, we suggest that strong SERT inhibitory properties of paroxetine might lead to a tonic suppressive influence on dopamine neurotransmission. This physiological link may explain an increase in prolactin levels through dopamine depletion in the tuberoinfundibular pathway.

No significant relationships.

The spread of the corona virus (COVID-19) has an enormous psychosocial impact on humanity across the globe, resulting in an increase in mental health issues. There are no specific diagnostic instruments that could identify COVID-19 related mental health problems. In recent months, new scales have been developed to identify COVID-19 related problems.

Our objective was to investigate the clinical utility of these new assessment instruments.

We performed a literature search, using Pubmed, EMBASE, Scopus and Cochrane library databases, to search for new scales identifying COVID-19 related mental health problems.

During the first half of the year 2020, we found five published new self-report measurement instruments: Coronavirus Anxiety Scale (CAS), the COVID Stress Scales (CSS), the Fear of COVID-19 Scale (FCV-19S), the Obsession with COVID-19 Scale (OCS), and the Questionnaire on Perception of Threat from COVID-19. These instruments have been validated in a group of middle-aged ambulatory patients.

These new instruments might be useful in non-clinical settings. Although the psychometric reports are promising, the instruments have been validated in a less vulnerable group of patients. Future validation studies should also comprise other age groups, particularly the old and more vulnerable population.

No significant relationships.

Psychotropic medications are frequently co-prescribed with antiretroviral therapy (ART). Hepatic metabolism both of AP and ART involves the cytochrome P450 enzyme system, potentially leading to a multitude of pharmacokinetic (PK) interactions and serious adverse side effects. The magnitude and clinical impact of PK-interactions can vary significantly.

The scope of this review is to summarize the currently available data regarding drug-drug interactions (DDI) between AP and ART, and to provide recommendations for their management.

A formal search of Embase, Cochrane and Medline was performed, searching for human studies from inception till 2017 on PK-interactions between AP and ART and reporting clinical toxicity as outcomes. Authors also provide their expertise on magnitude and clinical relevance of DDI using PK interaction chart.

Ten case reports including total of 13 patient were analyzed, comprising following AP: aripiprazole (N=2), risperidone (N=4), quetiapine (N=3) and lurasidone (N=1) in combination with various ART regiments. Significant PK-interactions were to occur in cases when aripiprazole was combined with ritonavir and/or cobicistat or efavirenz and/or darunavir; risperidone with indinavir of ritonavir; quetiapine with ritonavir and atazanavir/ritonavir; lurasidone with atazanavir. Adverse events occurred in combinations of aripiprazole with ritonavir/darunavir, risperidone with ritonavir or indinavir, quetiapine with atazanavir and lurasidone with atazanavir.

Psychotropics and antiretrovirals may be used safely, particularly when known DDIs are proactively managed. Clinicians should be aware of the pharmacokinetic and pharmacodynamic properties of these agents to best direct therapy and to provide optimal patient care

No significant relationships.

In recent years, more and more attention has been paid to the risks of using SSRIs. This group of antidepressants may be associated with an increased risk of gastrointestinal bleeding. This risk would be even further increased with concomitant use of NSAIDs. A number of studies have described this interaction, however they reported conflicting results.

Our objective was to investigate the risk of gastrointestinal bleeding with SSRIs, with or without NSAID use.

We performed a literature search, using Pubmed, EMBASE, and Cochrane library, in order to investigate controlled trials, cohort, case-control and cross-sectional studies that reported the incidence of gastrointestinal bleeding s on SSRIs with or without concurrent NSAID use, compared to placebo or no treatment.

15 case-control studies and 4 cohort studies were included in the analysis. There was an increased risk of gastrointestinal bleeding with SSRIs in the cohort studies and case-control studies. The risk of gastrointestinal bleeding was even further increased with the combined use of both SSRIs and NSAIDs.

SSRIs are associated with a modest increase of gastrointestinal bleeding. However, this risk is significantly increased when SSRIs are used in combination with NSAIDs. Psychiatrists should be aware of the hazards in prescribing these medications together.

No significant relationships.

Known risk factors for developing of first-time psychosis in patients with deep brain stimulator (DBS) include older age, short time after implant placement and cerebral target for stimulation. In particular, stimulation of subtalamic nucleus and globus pallidus internus has been shown to elicit psychotic symptoms in various case reports. To date, there are no cases describing onset of psychosis due to DBS in the ventralis intermediate nucleus (Vim) of the thalamus.

Case describtion of psychotic episode provoked by DBS in Vim region

Case report of 70 y.o. female with unilateral DBS from 2012 in Vim for essential tremor, who developed therapy resistant psychotic symptoms right after adjusted settings of the DBS.

Psychotic onset of otherwise healthy 70 y.o. patient occurred and gradually worsened after adjustment of DBS settings in absence of other iatrogenic factors, including medication and comorbidity, and required involuntary hospitalization one week after beginning of psychosis. Treatment after hospitalization comprised olanzapine 10 mg. 1dd1 did not cause resolvent of psychosis. Because of therapy resistance to psychofarmaca and worsening of psychotic symptoms, by way of exception neurologists had to change the settings back to basic leading to complete and sustained remission of psychosis within two days.

Among side effects of DBS in Vim, psychotic symptoms have never been reported. However, as in our patient, psychosis occurred after changes of settings in DBS and presented acutely, was severe, resulted in involuntary hospitalization and was therapy resistant. Pathophysiology of DBS-induced psychosis in Vim region is not known and requires further investigation.

No significant relationships.

Antepartum depressive symptoms (ADS) are highly prevalent and may affect the mother and child. Cognitive–behavioural therapy and interpersonal therapy are effective psychological interventions for depression. However, low adherence and high attrition rates in studies of prevention and treatment of antepartum depression suggest that these approaches might not be entirely suitable for women with mild/moderate ADS. Considering the protective association between resilience and ADS, women with ADS might benefit more from interventions focusing on promotion of mental well-being and resilience.

We aimed to provide an overview of studies evaluating the effectiveness of antepartum resilience-enhancing interventions targeting the improvement of ante- and postpartum depressive symptoms. We also investigated whether these interventions improve resilience and resilience factors in the peripartum period.

We conducted a systematic review, using PRISMA guidelines. Studies were eligible for inclusion when they utilised a randomised controlled trial or quasi-experimental design, studied pregnant women with ADS, and implemented psychological interventions that (a) aimed to reduce maternal ADS and/or prevent peripartum major depression, and (b) addressed one or more psychological resilience factors.

Five of the six included cognitive–behavioural therapy interventions and all four mindfulness-based interventions were effective in reducing peripartum depressive symptoms and/or the incidence of depression. However, the methodological quality of most of the included studies was low to moderate. Only three studies assessed change in resilience factors.

Resilience-enhancing interventions might be beneficial for mental well-being of pregnant women with ADS, although more rigorously designed intervention studies are needed.

People with psychotic disorders receive mental healthcare services mainly for their psychiatric care needs. However, patients often experience multiple physical or social wellbeing-related care needs as well. This study aims to identify care needs, investigate their changes over time and examine their association with mental healthcare consumption and evidence-based pharmacotherapy.

This study combined annually obtained routine outcome monitoring (ROM) data with care consumption data of people with a long-term psychotic illness receiving treatment in four Dutch mental healthcare institutes between 2012 and 2016. Existing treatment algorithms were used to determine psychiatric, physical and social wellbeing-related care needs based on self-report questionnaires, semi-structured interviews and physical parameters. Care consumption was measured in hours of outpatient mental healthcare consumption per year. Generalised estimating equation models were used to calculate odds ratios of care needs and their associations with time, mental healthcare consumption and medication use.

Participants (n = 2054) had on average 7.4 care needs per measurement and received 25.4 h of care per year. Physical care needs are most prevalent and persistent and people with more care needs receive more mental healthcare. Care needs for psychotic symptoms and most social wellbeing-related care needs decreased, whereas the chance of being overweight significantly increased with subsequent years of care. Several positive associations were found between care needs and mental healthcare consumption as well as positive relations between care needs and evidence-based pharmacotherapy.

This longitudinal study present a novel approach in identifying care needs and their association with mental healthcare consumption and pharmacotherapy. Identification of care needs in this way based on ROM can assist daily clinical practice. A recovery-oriented view and a well-coordinated collaboration between clinicians and general practitioners together with shared decisions about which care needs to treat, can improve treatment delivery. Special attention is required for improving physical health in psychosis care which, despite appropriate pharmacotherapy and increasing care consumption, remains troublesome.

The characteristics of patients who have repeated compulsory psychiatric admissions are largely unknown.

To investigate the frequency and risk factors for repeated emergency compulsory psychiatric admission (ECPA); and to identify targets for interventions to reduce repeated ECPA.

Data were collected from a database of electronic patient files (EPFs) held by three psychiatric emergency services (PES) in the Netherlands. Analyses were based on the data for adult patients (aged 18–75 years) with a first PES contact in 2010–2015. Using descriptive statistics and regression analysis, we studied the associations between baseline patient factors and repeated ECPA and time to readmission, within a 2-year follow-up period.

We included 6059 patients: 15.6% had two or more ECPAs. In total, 66% of second ECPAs had occurred within 6 months of the first. About 30% of all ECPAs were repeated ECPAs. Two baseline factors were associated with a higher frequency of a second ECPA: history of receiving any mental healthcare treatment, whether in-patient or out-patient or both, and a lower level of self-care. Three were associated with a lower frequency: ethnicity (other than Dutch), older age and suicidality. Lower Global Assessment of Functioning (GAF) scores and housing problems were associated with a shorter time to compulsory readmission and persistent psychiatric problems with a longer time to compulsory readmission.

We found that 15.6% of patients had two or more ECPAs. Two-thirds of the second ECPAs had occurred within 6 months of the first. Like earlier studies, the risk factors we identified suggest that interventions to reduce the risk of repeated compulsory psychiatric admission should seek to improve self-care, general daily functioning and homelessness.

John Farquhar Fulton was an American neurophysiologist and historian, who pioneered psychosurgery based on animal experiments. Together with psychologist Carlyle Jacobsen, Fulton presented the results of bilateral frontal lobe ablation in chimpanzees. This study prompted neurologist Egas Moniz and neurologist Walter Freeman to perform similar brain surgery on human subjects.

To present the scientific papers of John Farquhar Fulton on psychosurgery.

To review available literature and to show evidence that John Farquhar Fulton made a significant contribution to the development of psychosurgery.

A biography and research papers are presented and discussed.

Fulton and Jacobsen experimented with ‘delayed response tasks’ in chimpanzees. The aim was to test the animal's capability to memorize the correct location of the food. They found that after sequential ablations of the left and right frontal association cortices these memory tasks became significantly difficult for the monkeys to perform. The researchers saw parallel conclusions in clinical cases of human frontal lobe damage.

An investigation into the role of the limbic system is one of the crowning achievements of John Farquhar Fulton, as this has influenced even today's thinking about the role of the limbic system. We should thank Fulton for his pioneering work as modern psychosurgery has gradually evolved from irreversible ablation to reversible stimulation techniques, including deep brain stimulation.

The authors have not supplied their declaration of competing interest.

Due to the aging population worldwide, chronic pain is becoming an important public health concern. Chronic pain is bidirectional associated with psychiatric disorders including depression and anxiety. Antidepressants are widely used as adjuvant therapy for the treatment of chronic pain for many disorders.

To review available literature on the efficacy and safety of antidepressants for the treatment of chronic pain, including neuropathic pain, fibromyalgia, low back pain, and chronic headache or migraine.

We performed a detailed literature review through PubMed, EMBASE and Cochrane's Library to assess the efficacy and safety of antidepressants in chronic pain conditions.

In neuropathic pain, fibromyalgia, low back pain, and chronic headaches/migraine, tricyclic antidepressants (TCAs) showed a significant analgesic effect. Selective serotonin reuptake inhibitors (SSRIs) are not effective for the treatment of low back pain and headaches or migraine. Venlafaxine, a serotonin norepinephrine reuptake inhibitor (SNRI) showed significant improvement of fibromyalgia and neuropathic pain. Duloxetine (SNRI) also reduced the pain in fibromyalgia.

TCAs are the ‘gold standard’ antidepressant analgesics. However, an electrocardiogram and postural blood pressure should be implemented prior to TCA treatment and TCAs should be initiated at low dosages and subsequently increased to the maximum tolerated dose. One should pay attention to their cardiotoxic potential, especially in the older population. For the treatment of neuropathic pain, SNRIs are second-line agents. Although better tolerated, in most types of chronic pain conditions, the effectiveness of SSRIs is limited. To conclude: start low, go slow, and prescribe with caution.

The authors have not supplied their declaration of competing interest.

Older adults with adrenocortical insufficiency, including Addison's disease (AD), are at an increased risk for developing late-life depression. Treatment of AD with glucocorticoid replacement therapy may exacerbate depressive symptoms and may complicate treatment of late-life depression.

To present a case with algorithm of decision-making in a particular case of glucocorticoid induced depression in patient with syndrome of Addison.

To report a case-study, describing treatment of Addison's disease in LLD.

A case report is presented and discussed, followed by a literature review.

A 77-year-old female, diagnosed with Addison's disease, was referred with persistent fatigue, weakness, weight loss, sleep disturbances, and depressive symptoms over the previous 6 months. She was taken losartan 100 mg/day, zolpidem 10 mg/day, fludrocortisone 100 μg/day, and hydrocortisone 35 mg/day. There was no personal or family history of psychiatric problems. Clinical examination was normal aside from skin hyperpigmentation. After initial minimal dose reduction of glucocorticoids, Addison's disease remained under control. One week later, her depressive symptoms disappeared without administration of antidepressants.

The association between glucocorticoid replacement therapy and late-life depression is not well understood. The current case shows that treatment of glucocorticoid-induced depression in subjects with Addison's disease is achievable by minimal adjustments in glucocorticoid regiment. However, collaboration with endocrinology is of vital importance to prevent an Addison's crisis. Pharmacokinetic dose-finding studies are required to find optimal glucocorticoid adjustment strategy.

The authors have not supplied their declaration of competing interest.

In dementia, delusions are common with prevalence up to 75%. However, erotomanic delusions, or De Clerambault's syndrome, are a rarity in dementia. To date, only six case-reports have been described in vascular dementia, frontotemporal dementia, and Alzheimer's dementia.

To present a case of De Clerambault's syndrome in an older adult diagnosed with vascular dementia.

To review available literature on De Clerambault's syndrome in dementia.

A case report is presented and discussed followed by a literature review.

We report a 72-year-old female with a history of right posterior cerebral artery infarction. The patient developed a sudden onset erotomanic delusion after she met a male patient of her age during her stay in a dementia day care center. She was agitated, disorientated, presented with confabulation, and showed a dysphoric mood. On MMSE she scored 14/30, the clock-drawing test revealed visuospatial deficits. On MRI, the right occipital lobe showed an encephalomalacia. The patient was treated with sertraline 50 mg/day and olanzapine 5 mg/day. Her erotomanic delusions improved after 3 months of treatment.

De Clerambault's syndrome is a rare and poorly understood disorder with generally a poor response to treatment. Some cases were successfully treated with atypical anti-psychotics. However, further research is needed to explore the course and treatment of this delusion.

The authors have not supplied their declaration of competing interest.

José Manuel Rodriguez Delgado (1915–2011), a Spanish physiologist, was among the first scientist to perform electric brain stimulation in both animals and humans. His work on brain-stimulation research during the 1960s and 1970s was innovative but also controversial.

To present the scientific papers of Jose Delgado on psychosurgery.

To review available literature and to show evidence that Jose Delgado made a significant contribution to the development of psychosurgery.

A biography and private papers are presented and discussed followed by a literature review.

Delgado showed that with electrical brain stimulation one could evoke well-organized complex behavior in primates. A rhesus monkey was stimulated with an electrode implanted inside the red nucleus, followed by a complex sequence of events. After stimulation of an area three millimeters from the red nucleus, the rhesus monkey just yawned. Delgado also investigated the mechanisms of aggressive behavior in other animals. Stimulation of the caudate nucleus by remote control in a fighting bully resulted in sudden paralysis. In some human patients suffering from depression, euphoria was induced after stimulation of the septum.

Delgado pioneered the brain electrode implantation in order to electrically stimulate specific brain areas for treatment epilepsy and of different types of mental illness. He was severely criticized. His studies, however, paved the way for new modulation techniques such as the development of deep brain stimulation.

The authors have not supplied their declaration of competing interest.

Psychotropic agents have been implicated in the cause of hyponatremia, including the majority of selective serotonin reuptake inhibitors (SSRIs). The reported incidence of hyponatremia caused by SSRIs varies widely up to 40%. Important risk factors are older age and concomitant use of diuretics. Though there are numerous retrospective studies available, an update of current knowledge SSRI induced hyponatremia is warranted.

To review the incidence, risk factors, mechanism, times of onset and resolution, and treatment of hyponatremia associated with selective serotonin-reuptake inhibitors (SSRIs).

An English language literature search was conducted using Pubmed, EMBASE and Cochrane library (December 1980–December 2015) using the search terms selective serotonin-reuptake inhibitor, hyponatremia, syndrome of inappropriate secretion of antidiuretic hormone, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline.

Numerous case reports, observational studies, and case-controlled studies, as well as one prospective clinical trial, have reported hyponatremia associated with SSRI use, with an incidence of 15%. Risk factors for the development of hyponatremia with SSRIs include older age, female gender, and concomitant use of diuretics, low body weight, and lower baseline serum sodium concentration. Predisposing factors, such as volume status, diuretic use, or concomitant use of other agents known to cause SIADH, may predispose to the development of hyponatremia. In published reports, hyponatremia developed within the first few weeks of treatment and resolved within 2 weeks after therapy was discontinued.

Practitioners should be on the alert for this potentially life-threatening adverse event, especially in older adults.

The authors have not supplied their declaration of competing interest.

Walter Jackson Freeman II was born the grandchild of William Williams Keen, one of world's most renowned surgeons from Philadelphia and the son of an otorhinolaryngist, which may have been contributed to his interest in medicine. Freeman started his medical career in a psychiatric hospital and over the years, he operated thousands of patients. He was a protagonist in American psychosurgery and therefore, he often has been referred as the “lobotomist”.

To present the scientific papers of Walter Jackson Freeman on psychosurgery.

To review available literature and to show evidence that Freeman made a significant though controversial contribution to the development of psychosurgery.

A biography is presented and discussed followed by a literature review.

In this whole career, “the lobotomist” operated more than 3500 patients and performed mainly operations on the frontal areas. However, he operated human brains without due regard for his patient's mental abilities and emotional well-being after their lobotomy. Despite his work was praised, there was also a lot of criticism on his methods.

Despite the dubious reputation, Freeman can be remembered as an ambitious doctor who made a significant contribution to the development of psychosurgery. However, unfortunately he crossed medical and legal boundaries.

The authors have not supplied their declaration of competing interest.

For over 20 years, bupropion has been used as an antidepressant by inhibiting the norepinephrine-dopamine reuptake. Hyponatremia is a relatively rare condition that has been associated with the use of antidepressants including selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs). However, a few case studies have reported that bupropion was associated with hyponatremia.

To review available literature on bupropion-induced hyponatremia and its possible underlying mechanisms.

Case studies are presented and discussed followed by a literature review.

Hyponatremia has been reported with the use of many antidepressants, however, studies on bupropion induced hyponatremia has been limited. In literature only four case reports have been presented. Typically, this condition is only seen in frail or elderly patients. Possible mechanism is that bupropion may cause hyponatremia by the noradrenergic stimulation of vasopressin release.

Clinicians should be aware of increased risk of hyponatremia associated with antidepressants, including bupropion. Especially in the elderly, clinical symptoms of hyponatremia can be misinterpreted and may lead to a life-threatening condition.

The authors have not supplied their declaration of competing interest.