Antidepressant withdrawal – the tide is finally turning

Withdrawal reactions when coming off antidepressants have long been neglected or minimised. It took almost two decades after the selective serotonin reuptake inhibitors (SSRIs) entered the market for the first systematic review to be published. More reviews have followed, demonstrating that the dominant and long-held view that withdrawal is mostly mild, affects only a small minority and resolves spontaneously within 1–2 weeks, was at odd with the sparse but growing evidence base. What the scientific literature reveals is in close agreement with the thousands of service user testimonies available online in large forums. It suggests that withdrawal reactions are quite common, that they may last from a few weeks to several months or even longer, and that they are often severe. These findings are now increasingly acknowledged by official professional bodies and societies

Subclinical psychosis syndromes in the general population: results from a large-scale epidemiological survey among residents of the canton of Zurich, Switzerland

Aims. Prevalence and covariates of subclinical psychosis have gained increased interest in the context of early identification and treatment of persons at risk for psychosis. Methods. We analysed 9829 adults representative of the general population within the canton of Zurich, Switzerland. Two psychosis syndromes, derived from the SCL-90-R, were applied: 'schizotypal signs' and 'schizophrenia nuclear symptoms'. Results. Only a few subjects (13.2%) reported no schizotypal signs. While 33.2% of subjects indicated mild signs, only a small proportion (3.7%) reported severe signs. A very common outcome was no 'schizophrenia nuclear symptoms' (70.6%). Although 13.5% of the participants reported mild symptoms, severe nuclear symptoms were very rare (0.5%). Because these two syndromes were only moderately correlated (r = 0.43), we were able to establish sufficiently distinct symptom clusters. Schizotypal signs were more closely connected to distress than was schizophrenia nuclear symptoms, even though their distribution types were similar. Both syndromes were associated with several covariates, such as alcohol and tobacco use, being unmarried, low education level, psychopathological distress and low subjective well-being. Conclusions. Subclinical psychosis symptoms are quite frequent in the general population but, for the most part, are not very pronounced. In particular, our data support the notion of a continuous Wald distribution of psychotic symptoms in the general population. Our findings have enabled us to confirm the usefulness of these syndromes as previously assessed in other independent community samples. Both can appropriately be associated with well-known risk factors of schizophrenia

Injectivity of sections of convex harmonic mappings and convolution theorems

In the article the authors consider the class ${\mathcal H}_0$ of sense-preserving harmonic functions $f=h+\overline{g}$ defined in the unit disk $|z|<1$ and normalized so that $h(0)=0=h'(0)-1$ and $g(0)=0=g'(0)$, where $h$ and $g$ are analytic in the unit disk. In the first part of the article we present two classes $\mathcal{P}_H^0(\alpha)$ and $\mathcal{G}_H^0(\beta)$ of functions from ${\mathcal H}_0$ and show that if $f\in \mathcal{P}_H^0(\alpha)$ and $F\in\mathcal{G}_H^0(\beta)$, then the harmonic convolution is a univalent and close-to-convex harmonic function in the unit disk provided certain conditions for parameters $\alpha$ and $\beta$ are satisfied. In the second part we study the harmonic sections (partial sums) $$s_{n, n}(f)(z)=s_n(h)(z)+\overline{s_n(g)(z)},$$ where $f=h+\overline{g}\in {\mathcal H}_0$, $s_n(h)$ and $s_n(g)$ denote the $n$-th partial sums of $h$ and $g$, respectively. We prove, among others, that if $f=h+\overline{g}\in{\mathcal H}_0$ is a univalent harmonic convex mapping, then $s_{n, n}(f)$ is univalent and close-to-convex in the disk $|z|< 1/4$ for $n\geq 2$, and $s_{n, n}(f)$ is also convex in the disk $|z|< 1/4$ for $n\geq2$ and $n\neq 3$. Moreover, we show that the section $s_{3,3}(f)$ of $f\in {\mathcal C}_H^0$ is not convex in the disk $|z|<1/4$ but is shown to be convex in a smaller disk.Comment: 16 pages, 3 figures; To appear in Czechoslovak Mathematical Journa

How to Choose a Champion

League competition is investigated using random processes and scaling techniques. In our model, a weak team can upset a strong team with a fixed probability. Teams play an equal number of head-to-head matches and the team with the largest number of wins is declared to be the champion. The total number of games needed for the best team to win the championship with high certainty, T, grows as the cube of the number of teams, N, i.e., T ~ N^3. This number can be substantially reduced using preliminary rounds where teams play a small number of games and subsequently, only the top teams advance to the next round. When there are k rounds, the total number of games needed for the best team to emerge as champion, T_k, scales as follows, T_k ~N^(\gamma_k) with gamma_k=1/[1-(2/3)^(k+1)]. For example, gamma_k=9/5,27/19,81/65 for k=1,2,3. These results suggest an algorithm for how to infer the best team using a schedule that is linear in N. We conclude that league format is an ineffective method of determining the best team, and that sequential elimination from the bottom up is fair and efficient.Comment: 6 pages, 3 figure

No evidence of response bias in a populationbased childhood cancer survivor questionnaire survey-Results from the Swiss Childhood Cancer Survivor Study

Purpose This is the first study to quantify potential nonresponse bias in a childhood cancer survivor questionnaire survey. We describe early and late responders and nonresponders, and estimate nonresponse bias in a nationwide questionnaire survey of survivors. Methods In the Swiss Childhood Cancer Survivor Study, we compared characteristics of early responders (who answered an initial questionnaire), late responders (who answered after ≥1 reminder) and nonresponders. Sociodemographic and cancer-related information was available for the whole population from the Swiss Childhood Cancer Registry. We compared observed prevalence of typical outcomes in responders to the expected prevalence in a complete (100% response) representative population we constructed in order to estimate the effect of nonresponse bias. We constructed the complete population using inverse probability of participation weights. Results Of 2328 survivors, 930 returned the initial questionnaire (40%); 671 returned the questionnaire after ≥1reminder (29%). Compared to early and late responders, we found that the 727 nonresponders (31%) were more likely male, aged <20 years, French or Italian speaking, of foreign nationality, diagnosed with lymphoma or a CNS or germ cell tumor, and treated only with surgery. But observed prevalence of typical estimates (somatic health, medical care, mental health, health behaviors) was similar among the sample of early responders (40%), all responders (69%), and the complete representative population (100%). In this survey, nonresponse bias did not seem to influence observed prevalence estimates. Conclusion Nonresponse bias may play only a minor role in childhood cancer survivor studies, suggesting that results can be generalized to the whole population of such cancer survivors and applied in clinical practice

Mappings of least Dirichlet energy and their Hopf differentials

The paper is concerned with mappings between planar domains having least Dirichlet energy. The existence and uniqueness (up to a conformal change of variables in the domain) of the energy-minimal mappings is established within the class $\bar{\mathscr H}_2(X, Y)$ of strong limits of homeomorphisms in the Sobolev space $W^{1,2}(X, Y)$, a result of considerable interest in the mathematical models of Nonlinear Elasticity. The inner variation leads to the Hopf differential $h_z \bar{h_{\bar{z}}} dz \otimes dz$ and its trajectories. For a pair of doubly connected domains, in which $X$ has finite conformal modulus, we establish the following principle: A mapping $h \in \bar{\mathscr H}_2(X, Y)$ is energy-minimal if and only if its Hopf-differential is analytic in $X$ and real along the boundary of $X$. In general, the energy-minimal mappings may not be injective, in which case one observes the occurrence of cracks in $X$. Nevertheless, cracks are triggered only by the points in the boundary of $Y$ where $Y$ fails to be convex. The general law of formation of cracks reads as follows: Cracks propagate along vertical trajectories of the Hopf differential from the boundary of $X$ toward the interior of $X$ where they eventually terminate before making a crosscut.Comment: 51 pages, 4 figure

Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid

Caspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential activating platform for caspase-8 at the mitochondrial membrane surface. Destabilisation of this platform alters receptor-mediated apoptosis in diseases such as Barth Syndrome, which is characterised by the presence of immature cardiolipin which does not allow caspase-8 binding. We used a simplified in vitro system that mimics contact sites and/or cardiolipin-enriched microdomains at the outer mitochondrial surface in which the platform consisting of caspase-8, Bid and cardiolipin was reconstituted in giant unilamellar vesicles. We analysed these vesicles by flow cytometry and confirm previous results that demonstrate the requirement for intact mature cardiolipin for caspase-8 activation and Bid binding and cleavage. We also used confocal microscopy to visualise the rupture of the vesicles and their revesiculation at smaller sizes due to alteration of the curvature following caspase-8 and Bid binding. Biophysical approaches, including Laurdan fluorescence and rupture/tension measurements, were used to determine the ability of these three components (cardiolipin, caspase-8 and Bid) to fulfil the minimal requirements for the formation and function of the platform at the mitochondrial membrane. Our results shed light on the active functional role of cardiolipin, bridging the gap between death receptors and mitochondria

Straw blood cell count, growth, inhibition and comparison to apoptotic bodies

<p>Abstract</p> <p>Background</p> <p>Mammalian cells transform into individual tubular straw cells naturally in tissues and in response to desiccation related stress <it>in vitro</it>. The transformation event is characterized by a dramatic cellular deformation process which includes: condensation of certain cellular materials into a much smaller tubular structure, synthesis of a tubular wall and growth of filamentous extensions. This study continues the characterization of straw cells in blood, as well as the mechanisms of tubular transformation in response to stress; with specific emphasis placed on investigating whether tubular transformation shares the same signaling pathway as apoptosis.</p> <p>Results</p> <p>There are approximately 100 billion, unconventional, tubular straw cells in human blood at any given time. The straw blood cell count (SBC) is 45 million/ml, which accounts for 6.9% of the bloods dry weight. Straw cells originating from the lungs, liver and lymphocytes have varying nodules, hairiness and dimensions. Lipid profiling reveals severe disruption of the plasma membrane in CACO cells during transformation. The growth rates for the elongation of filaments and enlargement of rabbit straw cells is 0.6~1.1 (μm/hr) and 3.8 (μm³/hr), respectively. Studies using apoptosis inhibitors and a tubular transformation inhibitor in CACO2 cells and in mice suggested apoptosis produced apoptotic bodies are mediated differently than tubular transformation produced straw cells. A single dose of 0.01 mg/kg/day of p38 MAPK inhibitor in wild type mice results in a 30% reduction in the SBC. In 9 domestic animals SBC appears to correlate inversely with an animal's average lifespan (R²= 0.7).</p> <p>Conclusion</p> <p>Straw cells are observed residing in the mammalian blood with large quantities. Production of SBC appears to be constant for a given animal and may involve a stress-inducible protein kinase (P38 MAPK). Tubular transformation is a programmed cell survival process that diverges from apoptosis. SBCs may be an important indicator of intrinsic aging-related stress.</p