Due to the ongoing COVID-19 pandemic, an unprecedented number of people worldwide is currently affected by quarantine or isolation. These measures have been suggested to negatively impact on mental health. We conducted the first systematic literature review and meta-analysis assessing the psychological effects in both quarantined and isolated persons compared to non-quarantined and non-isolated persons. PubMed, PsycINFO, and Embase databases were searched for studies until April 22, 2020 (Prospero Registration-No.: CRD42020180043). We followed PRISMA and MOOSE guidelines for data extraction and synthesis and the Newcastle–Ottawa Scale for assessing risk of bias of included studies. A random-effects model was implemented to pool effect sizes of included studies. The primary outcomes were depression, anxiety, and stress-related disorders. All other psychological parameters, such as anger, were reported as secondary outcomes. Out of 6807 screened articles, 25 studies were included in our analyses. Compared to controls, individuals experiencing isolation or quarantine were at increased risk for adverse mental health outcomes, particularly after containment duration of 1 week or longer. Effect sizes were summarized for depressive disorders (odds ratio 2.795; 95% CI 1.467–5.324), anxiety disorders (odds ratio 2.0; 95% CI 0.883–4.527), and stress-related disorders (odds ratio 2.742; 95% CI 1.496–5.027). Among secondary outcomes, elevated levels of anger were reported most consistently. There is compelling evidence for adverse mental health effects of isolation and quarantine, in particular depression, anxiety, stress-related disorders, and anger. Reported determinants can help identify populations at risk and our findings may serve as an evidence-base for prevention and management strategies.

A ntidepressants are among the drugs most frequently prescribed not only in psychiatry but also other medical specialties. In 2017, 1.49 billion defined daily doses of antidepressants were prescribed in the health insurance system in Germany (not including private prescriptions and hospital treatments) (1). In addition to depression, they have also been approved for other indications such as anxiety and obsessive compulsive disorders. Sound knowledge of the side effects and risks of antidepressant medication is essential in order to inform and treat patients.Besides adverse drug reactions during antidepres sant use, adverse phenomena that occur following treatment discontinuation are increasingly becoming the focus of attention. Withdrawal phenomena of this kind were known as early on as in the early 1960s (2, e1). However, awareness of the significance of this topic remains low despite its considerable relevance. It is likely that a third of patients discontinue anti depressant medication within 1 month and 50% of patients by the end of the third month (e2), often without consulting their treating physician. A Danish study showed that the most frequent calls to a national medical advice hotline were accounted for by inquiries relating to antidepressant withdrawal phenomena (e3). It is essential, therefore, to provide patients at the start of treatment with relevant information on the risks of abrupt discontinuation, as recommended by the German clinical practice guidelines on unipolar depression (3).If adverse symptoms occur following discontinuation (or dose reduction) of treatment, a distinction needs to be made between withdrawal syndrome, rebound phenomena, and re-emergence of the primary disorder (Table 1).An accurate differential diagnosis is important, since it has crucial clinical consequences. For example, in the case of transient withdrawal phenomena, one can usually take a wait-and-see approach or treat symptomatically. In the case of disease recurrence, on the other hand, medication may need to be resumed. If pharmaceutical drugs are actually known to be associated with a risk of rebound following discontinuation, this needs to be taken into account as early on as at the time of making the indication and providing patient information.

Systematic reviews and meta-analyses suggest that there are increased rates of schizophrenia and related psychoses in firstand second-generation migrants and refugees. Here, we present a meta-analysis on the incidence of non-affective psychotic disorders among first-and second-generation migrants. We found substantial evidence for an increased relative risk of incidence among first-and second-generation migrants compared to the native population. As heterogeneity of included studies was high, effect estimates should be interpreted with caution and as guiding values rather than exact risk estimates. We interpret our findings in the context of social exclusion and isolation stress, and provide an explanatory framework that links cultural differences in verbal communication and experienced discrimination with the emergence of psychotic experiences and their neurobiological correlates. In this context, we discuss studies observing stress-dependent alterations of dopamine neurotransmission in studies among migrants versus non-migrants as well as in subjects with psychotic disorders. We suggest that social stress effects can impair contextualization of the meaning of verbal messages, which can be accounted for in Bayesian terms by a reduced precision of prior beliefs relative to sensory data, causing increased prediction errors and resulting in a shift towards the literal or "concrete" meaning of words. Compensatory alterations in higher-level beliefs, e.g., in the form of generalized interpretations of ambiguous interactions as hostile behavior, may contribute to psychotic experiences in migrants. We thus suggest that experienced discrimination and social exclusion is at the core of increased rates of psychotic experiences in subjects with a migration background.

IMPORTANCE This systematic review and meta-analysis is, to date, the first and most comprehensive to focus on the incidence of nonaffective psychoses among refugees.OBJECTIVE To assess the relative risk (RR) of incidence of nonaffective psychosis in refugees compared with the RR in the native population and nonrefugee migrants.

Antipsychotic-induced dopamine supersensitivity, or behavioral supersensitivity, is a problematic consequence of long-term antipsychotic treatment characterized by the emergence of motor abnormalities, refractory symptoms, and rebound psychosis. The underlying mechanisms are unclear and no approaches exist to prevent or reverse these unwanted effects of antipsychotic treatment. Here we demonstrate that behavioral supersensitivity stems from long-lasting pre, post and perisynaptic plasticity, including insertion of Ca2+-permeable AMPA receptors and loss of D2 receptor-dependent inhibitory postsynaptic currents (IPSCs) in D2 receptor-expressing medium spiny neurons (D2-MSNs) in the nucleus accumbens core (NAcore). The resulting hyperexcitability, prominent in a subpopulation of D2-MSNs (21%), caused locomotor sensitization to cocaine and was associated with behavioral endophenotypes of antipsychotic treatment resistance and substance use disorder, including disrupted extinction learning and augmented cue-induced cocaine-seeking behavior. Chemogenetic restoration of IPSCs in D2-MSNs in the NAcore was sufficient to prevent antipsychotic-induced supersensitivity, pointing to an entirely novel therapeutic direction for overcoming this condition.

Pericytes are vascular mural cells that surround capillaries of the central nervous system (CNS). They are crucial for brain development and contribute to CNS homeostasis by regulating blood–brain barrier function and cerebral blood flow. It has been suggested that pericytes are lost in Alzheimer's disease (AD), implicating this cell type in disease pathology. Here, we have employed state‐of‐the‐art stereological morphometry techniques as well as tissue clearing and two‐photon imaging to assess the distribution of pericytes in two independent cohorts of AD (n = 16 and 13) and non‐demented controls (n = 16 and 4). Stereological quantification revealed increased capillary density with a normal pericyte population in the frontal cortex of AD brains, a region with early amyloid β deposition. Two‐photon analysis of cleared frontal cortex tissue confirmed the preservation of pericytes in AD cases. These results suggest that pericyte demise is not a general hallmark of AD pathology.

Objective Avoiding withdrawal symptoms following antipsychotic discontinuation is an important factor when planning a safe therapy. We performed a systematic review and meta-analysis concerning occurrence of withdrawal symptoms after discontinuation of antipsychotics. Data Sources We searched the databases CENTRAL, Pubmed, and EMBASE with no restriction to the beginning of the searched time period and until October 1, 2019 (PROSPERO registration no. CRD42019119148). Study Selection Of the 18,043 screened studies, controlled and cohort trials that assessed withdrawal symptoms after discontinuation of oral antipsychotics were included in the random-effects model. Studies that did not implement placebo substitution were excluded from analyses. The primary outcome was the proportion of individuals with withdrawal symptoms after antipsychotic discontinuation. We compared a control group with continued antipsychotic treatment in the assessment of odds ratio and number needed to harm (NNH). Data Extraction We followed guidelines by the Cochrane Collaboration, PRISMA, and MOOSE. Results Five studies with a total of 261 individuals were included. The primary outcome, proportion of individuals with withdrawal symptoms after antipsychotic discontinuation, was 0.53 (95% CI, 0.37–0.70; I 2 = 82.98%, P < 0.01). An odds ratio of 7.97 (95% CI, 2.39–26.58; I 2 = 82.7%, P = 0.003) and NNH of 3 was calculated for the occurrence of withdrawal symptoms after antipsychotic discontinuation. Conclusion Withdrawal symptoms appear to occur frequently after abrupt discontinuation of an oral antipsychotic. The lack of randomized controlled trials with low risk of bias on antipsychotic withdrawal symptoms highlights the need for further research.

Social isolation and discrimination are growing public health concerns associated with poor physical and mental health. They are risk factors for increased morbidity and mortality and reduced quality of life. Despite their detrimental effects on health, there is a lack of knowledge regarding translation across the domains of experimental research, clinical studies, and real-life applications. Here, we review and synthesize evidence from basic research in animals and humans to clinical translation and interventions. Animal models indicate that social separation stress, particularly in early life, activates the hypothalamic-pituitary-adrenal axis and interacts with monoaminergic, glutamatergic, and GABAergic neurotransmitter systems, inducing long-lasting reductions in serotonin turnover and alterations in dopamine receptor sensitivity. These findings are of particular importance for human social isolation stress, as effects of social isolation stress on the same neurotransmitter systems have been implicated in addictive, psychotic, and affective disorders. Children may be particularly vulnerable due to lasting effects of social isolation and discrimination stress on the developing brain. The effects of social isolation and loneliness are pronounced in the context of social exclusion due to discrimination and racism, during widespread infectious disease related containment strategies such as quarantine, and in older persons due to sociodemographic changes. This highlights the importance of new strategies for social inclusion and outreach, including gender, culture, and socially sensitive telemedicine and digital interventions for mental health care.