[Stopping antidepressants: withdrawal symptoms and rebound effects : Review and practical recommendations]. / Absetzen von Antidepressiva ­ Absetzsymptome und Rebound-Effekte : Übersicht und praktische Empfehlungen.

Stopping antidepressants can cause withdrawal (discontinuation) symptoms, the return of the original illness, and rebound. The latter means that the disease will return stronger, faster, or with greater likelihood than if it had not been treated with medication. The Psychiatry Working Group of the Drug Commission of the German Medical Association (AkdÄ) presents the scientific findings and provides practical recommendations for action. Withdrawal symptoms are multiform; unspecific physical symptoms are predominant. Distinguishing them from the recurrence of depressive symptoms can be difficult. Most of them are mild and self-limiting. There is insufficient evidence on the extent and frequency of rebound depression. The rebound risk implies that when establishing the medication, the short-term benefit must be weighed against the possible long-term risk of chronic depression or the possible need for long-term medication. Patients should be informed about the risk of withdrawal both as early as the joint decision-making process about treatment initiation and regularly during the course of treatment. Withdrawal should take place gradually, except in emergency situations, whereby small steps should be taken, especially in the low-dose range.

Fourfold Differential Photoelectron Circular Dichroism.

We report on a joint experimental and theoretical study of photoelectron circular dichroism (PECD) in methyloxirane. By detecting O 1s photoelectrons in coincidence with fragment ions, we deduce the molecule's orientation and photoelectron emission direction in the laboratory frame. Thereby, we retrieve a fourfold differential PECD clearly beyond 50%. This strong chiral asymmetry is reproduced by ab initio electronic structure calculations. Providing such a pronounced contrast makes PECD of fixed-in-space chiral molecules an even more sensitive tool for chiral recognition in the gas phase.

Closed-loop recycling of rare liquid samples for gas-phase experiments.

Many samples of current interest in molecular physics and physical chemistry exist in the liquid phase and are vaporized for use in gas cells, diffuse gas targets, or molecular gas jets. For some of these techniques, the large sample consumption is a limiting factor. When rare, expensive molecules such as custom-made chiral molecules or species with isotopic labels are used, wasting them in the exhaust line of the pumps is quite an expensive and inefficient approach. Therefore, we developed a closed-loop recycling system for molecules with vapor pressures below atmospheric pressure. Once filled, only a few valves have to be adjusted, and a cold trap must be moved after each phase of recycling. The recycling efficiency per turn exceeds 95%.

Enantioselective fragmentation of an achiral molecule in a strong laser field.

Chirality is omnipresent in living nature. On the single molecule level, the response of a chiral species to a chiral probe depends on their respective handedness. A prominent example is the difference in the interaction of a chiral molecule with left or right circularly polarized light. In the present study, we show by Coulomb explosion imaging that circularly polarized light can also induce a chiral fragmentation of a planar and thus achiral molecule. The observed enantiomer strongly depends on the orientation of the molecule with respect to the light propagation direction and the helicity of the ionizing light. This finding might trigger new approaches to improve laser-driven enantioselective chemical synthesis.

Publisher Correction: Imaging the square of the correlated two-electron wave function of a hydrogen molecule.

The original version of this Article contained an error in the fifth sentence of the first paragraph of the 'Application on H2' section of the Results, which incorrectly read 'The role of electron correlation is quite apparent in this presentation: Fig. 1a is empty for the uncorrelated Hartree-Fock wave function, since projection of the latter wave function onto the 2pσu orbital is exactly zero, while this is not the case for the fully correlated wave function (Fig. 1d); also, Fig. 1b, c for the uncorrelated description are identical, while Fig. 1e, f for the correlated case are significantly different.' The correct version replaces 'Fig. 1e, f' with 'Fig. 2e and f'.

Imaging the square of the correlated two-electron wave function of a hydrogen molecule.

The toolbox for imaging molecules is well-equipped today. Some techniques visualize the geometrical structure, others the electron density or electron orbitals. Molecules are many-body systems for which the correlation between the constituents is decisive and the spatial and the momentum distribution of one electron depends on those of the other electrons and the nuclei. Such correlations have escaped direct observation by imaging techniques so far. Here, we implement an imaging scheme which visualizes correlations between electrons by coincident detection of the reaction fragments after high energy photofragmentation. With this technique, we examine the H2 two-electron wave function in which electron-electron correlation beyond the mean-field level is prominent. We visualize the dependence of the wave function on the internuclear distance. High energy photoelectrons are shown to be a powerful tool for molecular imaging. Our study paves the way for future time resolved correlation imaging at FELs and laser based X-ray sources.

Two-Particle Interference of Electron Pairs on a Molecular Level.

We investigate the photodouble ionization of H_{2} molecules with 400 eV photons. We find that the emitted electrons do not show any sign of two-center interference fringes in their angular emission distributions if considered separately. In contrast, the quasiparticle consisting of both electrons (i.e., the "dielectron") does. The work highlights the fact that nonlocal effects are embedded everywhere in nature where many-particle processes are involved.

Agreement of Experiment and Theory on the Single Ionization of Helium by Fast Proton Impact.

Even though the study of ion-atom collisions is a mature field of atomic physics, large discrepancies between experiment and theoretical calculations are still common. Here we present experimental results with high momentum resolution on the single ionization of helium induced by 1-MeV protons, and we compare these to theoretical calculations. The overall agreement is strikingly good, and even the first Born approximation yields good agreement between theory and experiment. This has been expected for several decades, but so far has not been accomplished. The influence of projectile coherence effects on the measured data is briefly discussed in terms of an ongoing dispute on the existence of nodal structures in the electron angular emission distributions.

Observation of electron energy discretization in strong field double ionization.

We report on the observation of discrete structures in the electron energy distribution for strong field double ionization of argon at 394 nm. The experimental conditions were chosen in order to ensure a nonsequential ejection of both electrons with an intermediate rescattering step. We have found discrete above-threshold ionization like peaks in the sum energy of both electrons, as predicted by all quantum mechanical calculations. More surprisingly, however, is the observation of two above-threshold ionization combs in the energy distribution of the individual electrons.

Evolution of interatomic Coulombic decay in the time domain.

During the past 15 years a novel decay mechanism of excited atoms has been discovered and investigated. This so-called interatomic Coulombic decay (ICD) involves the chemical environment of the electronically excited atom: the excitation energy is transferred (in many cases over long distances) to a neighbor of the initially excited particle usually ionizing that neighbor. It turned out that ICD is a very common decay route in nature as it occurs across van der Waals and hydrogen bonds. The time evolution of ICD is predicted to be highly complex, as its efficiency strongly depends on the distance of the atoms involved and this distance typically changes during the decay. Here we present the first direct measurement of the temporal evolution of ICD using a novel experimental approach.

Electron-nuclear energy sharing in above-threshold multiphoton dissociative ionization of H2.

We report experimental observation of the energy sharing between electron and nuclei in above-threshold multiphoton dissociative ionization of H2 by strong laser fields. The absorbed photon energy is shared between the ejected electron and nuclei in a correlated fashion, resulting in multiple diagonal lines in their joint energy spectrum governed by the energy conservation of all fragment particles.

Understanding the role of phase in chemical bond breaking with coincidence angular streaking.

Electron motion in chemical bonds occurs on an attosecond timescale. This ultrafast motion can be driven by strong laser fields. Ultrashort asymmetric laser pulses are known to direct electrons to a certain direction. But do symmetric laser pulses destroy symmetry in breaking chemical bonds? Here we answer this question in the affirmative by employing a two-particle coincidence technique to investigate the ionization and fragmentation of H2 by a long circularly polarized multicycle femtosecond laser pulse. Angular streaking and the coincidence detection of electrons and ions are employed to recover the phase of the electric field, at the instant of ionization and in the molecular frame, revealing a phase-dependent anisotropy in the angular distribution of H⁺ fragments. Our results show that electron localization and asymmetrical breaking of molecular bonds are ubiquitous, even in symmetric laser pulses. The technique we describe is robust and provides a powerful tool for ultrafast science.

Vibrationally resolved decay width of interatomic Coulombic decay in HeNe.

We investigate the ionization of HeNe from below the He 1s3p excitation to the He ionization threshold. We observe HeNe+ ions with an enhancement by more than a factor of 60 when the He side couples resonantly to the radiation field. These ions are an experimental proof of a two-center resonant photoionization mechanism predicted by Najjari et al. [Phys. Rev. Lett. 105, 153002 (2010)]. Furthermore, our data provide electronic and vibrational state resolved decay widths of interatomic Coulombic decay in HeNe dimers. We find that the interatomic Coulombic decay lifetime strongly increases with increasing vibrational state.

Early predictors of antisocial developmental pathways among boys and girls.

OBJECTIVE: We investigated in a high-risk sample the differential impact of biological and psychosocial risk factors on antisocial behaviour pathways. METHOD: One hundred and thirty-eight boys and 155 girls born at differing degrees of obstetric and psychosocial risk were examined from birth until adolescence. Childhood temperament was assessed by a highly-structured parent-interview and standardized behavioural observations, adolescent temperament was measured by self-report. Neurodevelopmental variables were assessed by age-specific developmental tests. Emotional and behaviour problems were measured at the ages of 8 and 15 by the Achenbach scales. RESULTS: In both genders, psychosocial adversity and early self-control temperament were strongly associated with early-onset persistent (EOP) antisocial behaviour. Psychosocial adversity and more severe externalizing problems differentiated the EOP from childhood-limited (CL) pathway. In girls, adolescent-onset (AO) antisocial behaviour was strongly associated with novelty seeking at 15 years. CONCLUSION: Our findings emphasize the need for early support and intervention in psychosocially disadvantaged families.

Risperidone-induced marked elevation of serum creatine kinase in adolescence. A case report.

We report on a 17-year-old boy who developed a marked increase in serum creatine kinase (CK) (9743 U/l) during treatment with risperidone for catatonic psychosis. Known causes of elevated CK such as delirium, malignant neuroleptic syndrome, infection, cocaine overdose, trauma, and intramuscular injections were ruled out. Vital signs remained always within the normal range. On discontinuation of risperidone, serum CK concentrations returned to 105 U/l within 1 week and remained within normal limits. While a transient moderate increase in CK activity at admission may be related to acute psychosis, risperidone seems to be the causative agent for the later marked elevation. To our knowledge, this is the first reported case of risperidone-associated elevation of serum CK in an adolescent. While discontinuation of risperidone does not seem necessary in patients with a moderate increase of serum CK, withdrawal of neuroleptics is warranted in more severe cases.

A clonal line of mesencephalic progenitor cells converted to dopamine neurons by hematopoietic cytokines: a source of cells for transplantation in Parkinson's disease.

Neural progenitor cells potentially provide a limitless, on-demand source of cells for grafting into patients with Parkinson's disease (PD) if the signals needed to control their conversion into dopamine (DA) neurons could be identified. We have recently shown that cytokines which instruct cell division and differentiation within the hematopoeitic system may provide similar functions in the central nervous system. We have shown that mitotic progenitor cells can be isolated from embryonic rat mesencephalon and that these cells respond to a combination of interleukin-1, interleukin-11, leukemia inhibitory factor, and glial cell line-derived neurotrophic factor yielding a tyrosine hydroxylase-immunoreactive (THir) phenotype in 20-25% of total cells. In the present study, 24 clonal cell lines derived from single cells of mesencephalic proliferation spheres were examined for their response to the cytokine mixture. The clone yielding the highest percentage of THir neurons (98%) was selected for further study. This clone expressed several phenotypic characteristics of DA neurons and expression of Nurr1. The response to cytokines was stable for several passages and after cryopreservation for several months. When grafted into the striatum of DA-depleted rats, these cells attenuated rotational asymmetry to the same extent as freshly harvested embryonic DA neurons. These data demonstrate that mesencephalic progenitor cells can be clonally expanded in culture and differentiated in the presence of hematopoietic cytokines to yield enriched populations of DA neurons. When transplanted, these cells provide significant functional benefit in the rat model of PD.

Diminished survival of mesencephalic dopamine neurons grafted into aged hosts occurs during the immediate postgrafting interval.

The survival rate of dopamine (DA) neurons in mesencephalic grafts to young adult rats is poor, estimated at 5-20%, and even poorer in grafts to the aged striatum. Grafted cells die in young adult rats during the first 4 days after implantation. The present study was undertaken to determine whether the decreased survival of DA neurons in grafts to aged rats is (1) due to additional cell death during the immediate postgrafting interval or (2) due to protracted cell loss during longer postgrafting intervals. We compared survival rates of tyrosine hydroxylase-immunoreactive (THir) neurons in cell suspension grafts to young adult (3 months) and aged (24 months) male Fischer 344 rats at 4 days and 2 weeks after transplantation. At 4 days after grafting, mesencephalic grafts within the aged rat striatum contain approximately 25% of the number of THir neurons in the same mesencephalic cell suspension grafted to young adult rats. This corroborates the decreased survival of grafted DA neurons we have demonstrated previously at 10 weeks postgrafting. THir neurons in grafts to the intact striatum possessed a significantly shorter "long axis" than their counterparts on the lesioned side. No significant differences in the number of apoptotic nuclear profiles or total alkaline phosphatase staining between mesencephalic grafts to young and aged rats were detectable at 4 days postgrafting. In summary, the present study indicates that the exaggerated cell death of grafted DA neurons that occurs following implantation to the aged striatum occurs during the immediate postgrafting interval, timing identical to that documented for young adult hosts.

Child development after maternal tocolysis with beta-sympathomimetic drugs.

The psycho-social development of both preterm and term children whose mothers reported tocolytic treatment was assessed at the ages of 2, 4.5, and 8 years. Term children exposed to tocolysis showed a higher rate of psychiatric disorders as well as poorer cognitive and motor performance than controls. In the preterm children no adverse impact of tocolysis could be found. The results are discussed concerning possible ways in which tocolytic treatment may influence child development. Restrictions because of the preliminary character of this study and the need of further prospective studies to clarify the developmental impact of tocolysis are also considered.

Time course of apoptotic cell death within mesencephalic cell suspension grafts: implications for improving grafted dopamine neuron survival.

The vast majority ( congruent with 90%) of embryonic mesencephalic dopamine (DA) neurons die following transplantation to the striatum. Recent reports indicate that at least a subpopulation of grafted cells undergo apoptotic cell death at early times following implantation. This study examines the temporal pattern and magnitude of apoptotic cell death following the implantation of mesencephalic cell suspension grafts. Two techniques, a modified terminal deoxynucleotide-mediated nucleotide end labeling (TUNEL) technique and cresyl violet staining, are used to assess apoptotic cell death by detection of its biochemical and morphological identifiers, respectively. Male, Fischer 344 rats were examined at 1, 4, 7, and 28 days following implantation of embryonic day 14 (E14) ventral mesencephalic cells to the DA-denervated striatum. Results indicate that the overwhelming majority of apoptotic cell death occurs within the first 7 days after transplantation. However, the impact of the apoptosis that occurs over the first week following grafting only appears to limit grafted tyrosine hydroxylase-immunoreactive (THir) neuron survival during the first 4 days. No significant differences between the survival rates of THir neurons at 4 days after grafting and at 28 days after grafting were found. Therefore, it appears that the critical interval during which an estimated 90% of grafted DA neurons die is during the first 4 days postimplantation and that a major contributor to this cell death is apoptosis.

Oligodendrocyte-type 2 astrocyte-derived trophic factors increase survival of developing dopamine neurons through the inhibition of apoptotic cell death.

Survival of embryonic dopamine (DA) neurons is extremely low (5-20%) following transplantation. Strategies to increase this survival are critical to the future of transplantation for Parkinson's disease. We demonstrate here that a factor(s) released from striatal oligodendrocyte-type 2 astrocytes (SO2A) greatly improves the survival and phenotype expression of mesencephalic DA neurons in culture while simultaneously decreasing the presence of apoptotic nuclear profiles, as detected by the TUNEL method and bisbenzamide/tyrosine hydroxylase double labeling. This SO2A-derived trophic factor(s) has minimal effects on glia and no effect on nondopaminergic mesencephalic neurons. The developmental period during which this SO2A trophic effect occurs (E14-18) coincides with the period when mesencephalic grafts are undergoing the highest rates of apoptosis, i.e., immediately following implantation. Therefore, SO2A-derived trophic factor(s) offers great potential for the augmentation of grafted DA neuron survival.