Psychiatric presentations and admissions during the first wave of Covid-19 compared to 2019 in a psychiatric emergency department in Berlin, Germany: a retrospective chart review.

BACKGROUND: Most studies agree that the Covid-19 pandemic and the subsequent lockdown had a negative impact on mental health. On the other hand, international studies have shown that psychiatric emergency departments (pED) experienced a decrease in presentations and admissions. METHODS: Retrospective chart review of all pED presentations and admissions during the first wave of Covid-19 pandemic in Germany (Covid-19 period: 3/2/20 to 05/24/20) in a psychiatric hospital in Berlin compared to 1 year earlier (pre-Covid-19 period). Descriptive statistics and logistic regression were performed. RESULTS: We observed no statistical significant changes in overall pED presentations and overall hospital admissions during the Covid-19 period compared to the pre-Covid-19 period (813 vs. 894, - 9.1%, p = 0.064 and (363 vs. 437, - 16.9%, p = 0.080 respectively). In the subgroup analysis, less patients with depressive disorders (p = 0.035) and with personality disorders (p = 0.002) presented to the pED, a larger number of presentations with schizophrenia was observed (p = 0.020). In the Covid-19 period, less patients with substance use disorder and paranoid schizophrenia were admitted to the hospital via the pED than in the pre-Covid-19 period (p = 0.035 and p = 0.006, respectively). Bed capacity was reduced in the Covid-19 period by - 32.8% (p <  0.001). Presentations in police custody were 13.7% (p = 0.029) higher during the Covid-19 compared to pre-Covid-19 period, with higher rates in female presentations (p = 0.008) and suicide attempts (p = 0.012) and less hospital admissions (p = 0.048). Logistic regression analyses revealed that positive predictors for pED presentation during Covid-19 period were police custody (p <  0.001), being redirected from another hospital (p <  0.001), suicide attempt (p = 0.038), suicidal thoughts (p = 0.004), presentation with paranoid schizophrenia (p = 0.001) and bipolar and manic disorders (p = 0.004), negative predictors were hospital admission (p <  0.001), depressive disorders (p = 0.021) and personality disorders (p <  0.001). CONCLUSIONS: A larger number of presentations in police custody during the Covid-19 period may represent untreated medical needs. This was seen predominantly in female patients, suggesting this subgroup might have suffered particularly under lockdown measures. Patients with paranoid schizophrenia were the only subgroup, which increased in absolute numbers, also suggesting a particular lockdown effect. Reduced bed capacity due to infection curbing measures is suggestive to have played an important role in augmenting the threshold for hospital admissions.

rTMS affects working memory performance, brain activation and functional connectivity in patients with multiple sclerosis.

OBJECTIVE: To investigate the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) on working memory performance, while measuring task-related brain activation and task-related brain connectivity in patients with multiple sclerosis (MS). METHODS: 17 patients with MS and 11 healthy controls (HCs) underwent 3 experimental sessions (baseline, real-rTMS, sham-rTMS), all including an N-back task (3 task loads: N1, N2, N3; control condition: N0) inside the MR scanner. Prior to imaging, real-rTMS (10 Hz) was applied to the right DLPFC. The stimulation site was defined based on individually assessed N-back task activation at baseline and located using neuronavigation. Changes in whole brain functional activation and functional connectivity with the right DLPFC were calculated. RESULTS: N-back task accuracy (N2 and N3) improved after real-rTMS (and not after sham-rTMS) compared with baseline (p=0.029 and p=0.015, respectively), only in patients. At baseline, patients with MS, compared with HCs, showed higher task-related frontal activation (left DLPFC, N2>N0), which disappeared after real-rTMS. Task-related (N1>N0) functional connectivity between the right DLPFC and the right caudate nucleus and bilateral (para)cingulate gyrus increased in patients after real-rTMS when compared with sham stimulation. CONCLUSIONS: In patients with MS, N-back accuracy improved while frontal hyperactivation (seen at baseline relative to HCs) disappeared after real-rTMS. Together with the changes in functional connectivity after real-rTMS in patients, these findings may represent an rTMS-induced change in network efficiency in patients with MS, shifting patients' brain function towards the healthy situation. This implicates a potentially relevant role for rTMS in cognitive rehabilitation in MS.

Depletion of murine T cells by in vivo monoclonal antibody treatment is enhanced by adding an autologous anti-rat kappa chain antibody.

In vivo treatment with monoclonal antibodies can be used for elimination of various T lymphocyte subsets from peripheral lymphoid organs and blood and thereby be used both to analyze the role of different T cells in immunoregulation and for the treatment of experimental immunological diseases. However, one problem with this approach has been that not all monoclonal antibodies given in vivo eliminate their target cells. We now show in the murine system that the normally inefficiently depleting H129.19 (anti-CD4) and 53.6.7 (anti-CD8) antibodies can be used for efficient depletion of their respective target cells when combined with injection of a secondary mouse anti-rat kappa (MAR18.5) antibody. The efficacy of the depletion protocols was ascertained by double staining techniques and cytofluorometric analysis. It is suggested that the presently used sandwich method applying a homologous secondary monoclonal antibody may provide an alternative to class switching or other manipulations of primary antibodies in increasing the efficacy of in vivo antibody treatment.

Activated type II collagen reactive T cells are not eliminated by in vivo anti-CD4 treatment. Implications for therapeutic approaches on autoimmune arthritis.

Activation of CD4+ T cells plays an important role in type II collagen (CII) induced arthritis (CIA). The CD4+ T cell dependency is demonstrated by anti-CD4 antibody treatment which suppresses CIA in mice if injected before CII immunization. The same anti-CD4 treatment at a later stage does not suppress CIA, despite extensive elimination of peripheral CD4+ T cells. A possible explanation for this discrepancy is that activated T cells might not be as easily influenced by the anti-CD4 antibodies as resting T cells. To address this question, the proliferative capacity of CII reactive CD4+ lymph node (LN) T cells, in mice treated with anti-CD4 antibodies before or after the CII immunization, was analyzed. In mice treated before immunization the capacity of LN cells to proliferate in vitro was markedly suppressed while in mice receiving anti-CD4 treatment after immunization it was retained. Flow cytometric analysis revealed that the anti-CD4 treatment before and after immunization reduced the number of CD4+ LN T cells to the same level. The small population of CD4+ LN cells which were left after anti-CD4 treatment of naive mice all expressed CD44, a marker for previously activated T cells in mice. We propose that activation render CII reactive T cells more resistant to anti-CD4 treatment than virgin T cells are and suggest that the lack of therapeutic effect of late anti-CD4 treatment in CIA does not necessarily implicate that CD4+ T cells are unimportant in that stage of the disease.

Drug intake and the dexamethasone suppression test.

The dexamethasone suppression test (DST) is being used clinically as a diagnostic laboratory test for depression. Drug histories collected from 336 psychiatric inpatients revealed that 60% were taking one or more drugs suspected of altering DST results in either a false-positive or false-negative manner. Practical limitations of the DST as a biologic marker of affective syndromes in relation to patient drug use are discussed.

Collagen induced arthritis as an experimental model for rheumatoid arthritis. Immunogenetics, pathogenesis and autoimmunity.

The type II collagen (CII) induced arthritis animal model (CIA) provides opportunities to study the nature of autoimmune reactions leading to arthritis and may be used as a model for rheumatoid arthritis (RA). Thus, in similarity with RA, the CIA model, when induced with autologous CII, shows a chronic and progressive disease course. The susceptibility to both RA and CIA are correlated to the expression of certain MHC class II allotype genes. In both diseases are autoantibodies to CII and rheumatoid factors produced. Immunohistopathology of affected joints show in both diseases a dominance of activated macrophages/fibroblasts with a significant infiltration of activated T cells and an infiltration of granulocytes. We do here suggest that both RA and CIA are dependent on a synergy between delayed type hypersensitivity and immune complex mediated inflammatory mechanisms and that CIA provides opportunities for studies of immunospecific reactions leading to arthritis.

Collagen induced arthritis: an experimental model for rheumatoid arthritis with involvement of both DTH and immune complex mediated mechanisms.

The type II collagen induced arthritis animal model (CIA) provides opportunities to study the nature of autoimmune reactions leading to arthritis and is also a useful model for rheumatoid arthritis (RA). Thus, in similarity with RA, the CIA when induced with autologous type II collagen, shows a chronic and progressive disease course. The susceptibility to both RA and CIA are correlated to the expression of certain MHC class II allotype genes. In both diseases autoantibodies to type II collagen and rheumatoid factors are produced. Immunohistopathology of affected joints show in both diseases a dominance of activated macrophages/fibroblasts with a significant infiltration of activated T cells. We suggest here that both RA and CIA are dependent on a synergy between delayed type hypersensitivity and immune complex mediated inflammatory mechanisms and that CIA could provide a tool for studies of immunospecific reactions leading to arthritis.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters intrathymic T-cell development in mice.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was administered to 2-4-week-old mice (5, 25, and 50 micrograms/kg body wt.) and to in vitro cultures (10(-9) M) of fetal thymi. By monitoring thymocyte populations with respect to the differentiation antigens CD4 and CD8, it was found that the cell number in all thymocyte populations except for CD8+ decreased significantly compared with controls. In vivo the most marked decrease occurred among double negative (DN) and double positive (DP) cells, whereas in vitro, the DP cells were most severely affected. The cell number had already decreased to some extent by day 1 after a dose of 50 micrograms/kg body wt. of TCDD, although a severe reduction did not become apparent until day 4. There was a clear dose/response relationship between 5 and 50 micrograms/kg body wt. Autoradiography and liquid scintillation counting studies showed that incorporation of [3H]thymidine in the thymus had already decreased 24 h after TCDD treatment, with the decrease being even more pronounced at 48 h. By 96 h, the rate of cell proliferation had returned to approximately normal values. The results show that TCDD has a long-lasting effect on thymocyte abundance together with a transient effect on cell proliferation. This indicates that in addition to the initial effects of TCDD on cell proliferation, it may also more permanently disturb the normal process of elimination by means of selection.

Early intervention with Portuguese mothers: a 2-year follow-up.

Results of a 2-year follow-up after an early intervention with low-middle-class primiparous Portuguese mothers are presented. On the 3rd day of their infants' lives, 40 mothers underwent a structured intervention using selected items of the Brazelton Neonatal Behavioral Assessment Scale. An additional 20 mothers randomized to the control group had a talk with a pediatrician about general problems of infant health care. On Day 28, the "sensory orientation" and "cuddliness" competencies of the infants in the experimental group were significantly enhanced when compared with the same competencies among the infants in the control group. In addition, dyads in the experimental group had established a more favorable pattern of interaction, particularly after short stressful situations (these situations included short separations from the mother in which a stranger was present, short separations in which no one was present, and a stillface situation). Short-term effects (the first month of life) were particularly noticeable, especially in terms of the babies' neurobehavioral development and mother-infant interaction. Long-term effects (3, 6, 9, 12, 15, 18, and 24 months), though less clear, were evident in the form of better interactive patterns among the dyads in the experimental group. This was particularly evident after the stressful situations to which they were submitted. These results are discussed in terms of both their scope and their clinical impact.

Behavioral science in medical education: a bibliography.

Since 1956, there have appeared 125 studies which focus on the issue of integrating behavioral science into undergraduate and graduate medical education.

Behavioral science in medical education: an updated bibliography.

Holmes, et al. in 1979 compiled 125 studies in a bibliography of behavioral science in undergraduate and graduate education. Since 1979, 75 additional studies of behavioral science in medical education have been identified. The current updated bibliography contains 200 entries. Foreign medical journals, Index Medicus, and Psychological Abstracts were reference sources for the bibliography.

Remyelination capacity of the MS brain decreases with disease chronicity.

OBJECTIVE: To analyze and compare the extent of remyelination in lesions from patients with multiple sclerosis (MS) who have a short (early MS lesions) or a long (chronic MS lesions) disease duration and to determine the influence of anatomic localization on the extent of remyelination. In early MS lesions, remyelination has been described as a relatively frequent event, in contrast to chronic MS lesions, where remyelination is absent or limited to the lesion border in the majority of lesions. However, no studies have been published that have quantified and compared the extent of remyelination in early and chronic MS lesions. METHODS: We analyzed the occurrence of remyelination in 52 biopsies from 51 patients (early MS) and in 174 lesions from 36 autopsy cases (chronic MS) by immunohistochemistry for myelin proteins, and correlated our findings with anatomic localization, sex, age, and disease duration. RESULTS: Significantly more lesions were remyelinated in early than in chronic MS (80.7% vs 60%). In chronic MS, subcortical lesions showed more extensive remyelination than periventricular lesions. The majority of cerebellar lesions were completely demyelinated. CONCLUSION: In summary, our data demonstrate that remyelination is a frequent event in early multiple sclerosis lesions. Furthermore, the anatomic localization of a lesion might influence the extent of remyelination.

Gender differences in the histopathology of MS?

Multiple sclerosis (MS) lesions are histopathologically characterized by inflammation, demyelination/remyelination, axonal damage and gliosis. Animal experimental and in vitro studies suggest that sex hormones influence the immune system and contribute to the increased likelihood in women of developing MS. However, a variety of studies have also shown that remyelination is more marked in female rodents or that female sex hormones are beneficial for myelin repair. To determine whether gender influences the histopathology of MS lesions, we compared the extent of inflammation, axonal damage and remyelination in MS lesions of female and male MS patients. We observed no differences in the composition of inflammatory infiltrates, axonal damage or cortical pathology. Similar numbers of oligodendroglial progenitor cells and mature oligodendrocytes were present in MS lesions. Remyelination is slightly, but not significantly, more extensive in women than men in early MS lesions. The absence of significant differences in lesion pathology between female and male MS patients might be explained by a lack of a gender influence, but also might be due to the limited number of tissue samples available for histopathological analysis.

Loxapine in the treatment of psychotic-depressive disorders: Measurement of antidepressant metabolites.

Psychotic patients who also have endogenous depressive symptoms often require treatment with several drugs (usually a neuroleptic-antidepressant combination) or electroconvulsive therapy. Loxapine is a neuroleptic of the dibenzoxazepine class; it is metabolized in vivo to desmethylloxapine (amoxapine) and 8-hydroxyamoxapine, two compounds with antidepressant activity. We traced the serum levels of total amoxapine (amoxapine plus 8-hydroxyamoxapine) in two treatment-resistant patients with psychotic-depression syndromes. One patient was treated with loxapine alone and the other with a loxapine-amoxapine combination. We also determined the total loxapine and amoxapine serum levels of ten patients treated at various dosages of loxapine alone. The results demonstrate that many patients treated with loxapine attain substantial serum levels of total amoxapine, some in concentrations thought to be therapeutic for nonpsychotic endogenous depression. We recommend further studies to determine the efficacy of loxapine in the management of treatment-resistant patients with psychotic-depression syndromes.

Depression in the elderly: a beta-adrenergic receptor dysfunction?

Depression is a significant problem in the elderly population and is often accompanied by cognitive changes and agitation. Hypothalamic-pituitary axis dysfunction may occur in some depressed elderly patients and represent a non-specific physiological hyperarousal state. Moreover, recent evidence confirms that antidepressants down-regulate beta-adrenergic receptors in the central nervous system. These findings provide the background for proposing that depression may result from an age-specific, stress-induced dysfunction of the beta-adrenergic receptor system in a subgroup of the geriatric population. A bio-psycho-social model for understanding and developing innovative treatment strategies for depression in the elderly is presented.

Anti-T cell receptor antibody treatment of rats with established autologous collagen-induced arthritis: suppression of arthritis without reduction of anti-type II collagen autoantibody levels.

Activation of T cells is critical for the development of type II collagen (CII)-induced arthritis (CIA). However, the relative importance of T cells in their delivery of help to B cells, promoting autoantibody formation or acting as inflammatory initiating cells, is unclear. The effect of a monoclonal antibody directed to the alpha/beta T cell receptor (TcR) on the development of autologous CIA was studied. Two weeks after immunization with autologous CII the onset of severe arthritis occurred, followed by a chronic arthritis activity in the peripheral joints. Anti-TcR treatment before immunization suppressed the incidence of arthritis and the autoantibody response to CII. Treatment given immediately before the expected onset delayed the appearance of arthritis. Treatment given to already arthritic rats reduced the severity. In the latter two groups the serum levels of anti-CII autoantibodies were not affected. The duration of the ameliorating effect was limited and with the return of arthritis a concomitant antibody response towards the injected mouse anti-TcR antibody was observed. These results show that the role of T cells in both the induction and perpetuation of CIA is essential and not limited to the triggering of production of pathogenic anti-CII autoantibodies.