Intergenerational transmission of adverse childhood experiences via maternal depression and anxiety and moderation by child sex.

Adverse childhood experiences (ACEs) of parents are associated with a variety of negative health outcomes in offspring. Little is known about the mechanisms by which ACEs are transmitted to the next generation. Given that maternal depression and anxiety are related to ACEs and negatively affect children's behaviour, these exposures may be pathways between maternal ACEs and child psychopathology. Child sex may modify these associations. Our objectives were to determine: (1) the association between ACEs and children's behaviour, (2) whether maternal symptoms of prenatal and postnatal depression and anxiety mediate the relationship between maternal ACEs and children's behaviour, and (3) whether these relationships are moderated by child sex. Pearson correlations and latent path analyses were undertaken using data from 907 children and their mothers enrolled the Alberta Pregnancy Outcomes and Nutrition study. Overall, maternal ACEs were associated with symptoms of anxiety and depression during the perinatal period, and externalizing problems in children. Furthermore, we observed indirect associations between maternal ACEs and children's internalizing and externalizing problems via maternal anxiety and depression. Sex differences were observed, with boys demonstrating greater vulnerability to the indirect effects of maternal ACEs via both anxiety and depression. Findings suggest that maternal mental health may be a mechanism by which maternal early life adversity is transmitted to children, especially boys. Further research is needed to determine if targeted interventions with women who have both high ACEs and mental health problems can prevent or ameliorate the effects of ACEs on children's behavioural psychopathology.

A randomized, double-blind, placebo-controlled trial of tegaserod in female patients suffering from irritable bowel syndrome with constipation.

BACKGROUND: Irritable bowel syndrome is a common functional gastrointestinal disorder which affects up to 20% of the population, with a predominance in females. AIM: To evaluate the efficacy and safety of tegaserod in female patients with irritable bowel syndrome characterized by symptoms of abdominal pain/discomfort and constipation. METHODS: In a randomized, double-blind, multicentre study, 1519 women received either tegaserod, 6 mg b.d. (n = 767), or placebo (n = 752) for 12 weeks, preceded by a 4-week baseline period without treatment and followed by a 4-week open withdrawal period. The primary efficacy evaluation was the patient's symptomatic response as measured by the Subject's Global Assessment of Relief. Other efficacy variables included abdominal pain/discomfort, bowel habits and bloating. RESULTS: Tegaserod produced significant (P < 0.05) improvements in the Subject's Global Assessment of Relief and other efficacy variables. These improvements were seen within the first week, and were maintained throughout the treatment period. After withdrawal of treatment, the symptoms rapidly returned. Overall, tegaserod was well tolerated. Diarrhoea was the most frequent adverse event; however, this led to discontinuation in only 1.6% of tegaserod-treated patients. CONCLUSIONS: Tegaserod, 6 mg b.d., produced rapid and sustained improvement of symptoms in female irritable bowel syndrome patients and was well tolerated.

Trauma and deferred action in the reality of adolescence.

In the search for ever earlier determinants of adult pathology many ignore the transformative impact of adolescence. The authors suggest that the reality of adolescent development creates a vulnerability to being overwhelmed. Through deferred action childhood experiences may interact with adolescent realities and omnipotent beliefs to traumatize the adolescent. The authors suggest that trauma in adolescence can be independent both of the intensity of current external exposure or of earlier traumatic experiences.

Love in the therapeutic alliance.

Volumes have been written about the patient's love for the therapist, but there has been relatively little discussion of the therapist's love for the patient. In an attempt to create a theoretical and technical space for discussing the appropriateness and role of love in the therapeutic relationship, a revised concept of the therapeutic alliance is applied to provide technical guidelines and understanding of two kinds of love between patient and therapist, corresponding to two systems of self-esteem regulation: an open, reality-oriented system and a closed, sadomasochistic system organized according to omnipotent beliefs. Examples of the role of love through the phases of treatment illustrate the interrelationship of love and the accomplishment of therapeutic alliance tasks.

A parametric approach to orthographic processing in the brain: an fMRI study.

Brain activation studies of orthographic stimuli typically start with the premise that different types of orthographic strings (e.g., words, pseudowords) differ from each other in discrete ways, which should be reflected in separate and distinct areas of brain activation. The present study starts from a different premise: Words, pseudowords, letterstrings, and false fonts vary systematically across a continuous dimension of familiarity to English readers. Using a one-back matching task to force encoding of the stimuli, the four types of stimuli were visually presented to healthy adult subjects while fMRI activations were obtained. Data analysis focused on parametric comparisons of fMRI activation sites. We did not find any region that was exclusively activated for real words. Rather, differences among these string types were mainly expressed as graded changes in the balance of activations among the regions. Our results suggest that there is a widespread network of brain regions that form a common network for the processing of all orthographic string types.

An application of the concept of the therapeutic alliance to sadomasochistic pathology.

This paper traces the history of the therapeutic alliance concept, examining how it has been used and misused, at times elevated to a central position and at others rejected altogether. The loss of this concept created a vacuum in classical psychoanalysis that has been filled by rival theories. The continuing usefulness of looking at the treatment process through the lens of the therapeutic alliance, particularly in relation to the manifold difficulties of working with sadomasochistic pathology, is suggested. To this end, revisions of the theory of the therapeutic alliance are suggested to address some of the difficulties that have arisen in conceptualizing this aspect of the therapeutic relationship, and to provide an integrated dynamic model for working with patients at each phase of treatment. This revised model acknowledges the complexity of the domain and encompasses the multiple tasks, functions, partners, and treatment phases involved. The utility of the revised theory is illustrated in application to understanding the sadomasochistic, omnipotent resistances of a female patient through the phases of her analysis.

Differential clearance of glycoforms of IgG in normal and autoimmune-prone mice.

In order to understand better the origins of the elevated levels of the glycoform of IgG that lacks galactose on both arms of the oligosaccharide chain (G0%) located in the Fc, which occurs in man and mouse with age, and in particular in autoimmune disease, we investigated the clearance of two glycosylated forms of IgG2a and IgG1 in normal (BALB/c) and autoimmune-prone (MRL/1pr, MRL/+, and non-obese diabetic (NOD)) mice. To investigate the possibility of different rates of catabolism, enzymatically generated glycoforms of monomeric IgG1 and IgG2a (fully glycosylated or G0%), were iodinated and injected into the tail vein of the mice. We found that the G0% IgG2a remained in circulation significantly longer than the fully glycosylated variants, in all of the mouse strains tested. In contrast, the two forms of IgG1 had similar kinetics in all the autoimmune-prone mice, whereas in BALB/c, there was a longer half-life (t1/2) for G0% IgG1. These data suggest that there may be differences in the ability of the IgG glycoforms to bind to the Fc gamma receptors, in particular Fc gamma RI. The clearance rates were found to vary among the strains studied, with MRL/1pr having the fastest catabolic rates for all glycoforms and IgG subclasses tested. This appeared to be due to the presence of circulating IgG and IgM rheumatoid factors (RF). There were significantly increased frequencies and titres for both IgM and IgG RF in MRL/1pr mice compared with the other strains. In contrast, interferon-gamma, known to induce the Fc gamma RI, was found to be similar in the sera, in all of the strains of mice examined. These results suggest that RF probably play an important biological function in the MRL/1pr mice and aid in the clearance of circulating IgG. Our study shows that the state of glycosylation of IgG affects the t1/2 in vivo, and that by removing the terminal sugars (sialic acid and galactose), the antibody (IgG2a) will remain in circulation significantly longer. These observations may thus provide a partial explanation for the increase in relative percentage of this glycoform that occurs with age.

Postoedipal transformations: latency, adolescence, and pathogenesis.

There is a tendency in psychoanalysis to seek ever earlier determinants of pathology. One effect of this search is to relegate adult memories of latency and adolescence to serving mainly a defensive screen function. Psychoanalytic material from child and adolescent cases is used in this paper to illuminate postoedipal developmental transformations. These findings are applied to the understanding and technique of work with adults. Alertness to latency elements can affect the timing of interpretations, the understanding of neurosogenic factors, and the forces for health available in the patient's personality. Alertness to adolescent phenomena highlights the adult patient's difficulty in integrating adolescent realities with childhood fantasy solutions to preoedipal and oedipal conflicts. We conclude that no one phase has preeminence over others, that earlier is not necessarily more important, and that there cannot be pure recapitulation, revival, or "reanimation" (Freud, 1925) of the past in the present. However, knowledge of the transformations appropriate to each phase in the past gives us additional access to the determinants and functions of the patient's pathology in the present, increases the specificity of genetic interpretation, and gives both patient and analyst greater conviction about the accuracy of the essential analytic work of reconstruction.

Purification, characterization, and biosynthesis of margatoxin, a component of Centruroides margaritatus venom that selectively inhibits voltage-dependent potassium channels.

A novel peptidyl inhibitor of K+ channels has been purified to homogeneity from venom of the new world scorpion Centruroides margaritatus. The primary structure of this 39-amino-acid peptide, which we term margatoxin (MgTX), was determined by amino acid compositional analysis and peptide sequencing. Margatoxin potently inhibits binding of radiolabeled charybdotoxin (ChTX) to voltage-activated channels in brain synaptic plasma membranes. Like ChTX, MgTX blocks the n-type current of human T-lymphocytes (Kv1.3 channel), but compared to ChTX, is 20-fold more potent (half-block at approximately 50 pM), has a slower dissociation rate, and has no effect on calcium-activated channels. To demonstrate that these characteristics are due solely to the purified toxin, recombinant MgTX was expressed in Escherichia coli as part of a fusion protein. After cleavage and folding, purified recombinant MgTX displayed the same properties as native peptide. Replacement of the COOH-terminal histidine residue of MgTX with asparagine resulted in a peptide with a 10-fold reduction in potency. This was due to a faster apparent dissociation rate, suggesting that the COOH-terminal amino acid may play an important role in the binding of MgTX to the Kv1.3 channel. MgTX displays significant sequence homology with previously identified K+ channel inhibitors (e.g. ChTX, iberiotoxin, noxiustoxin, and kaliotoxin). However, given its potency and unique selectivity, MgTX represents an especially useful tool with which to study the physiologic role of Kv1.3 channels.

Some comments on masochism and the delusion of omnipotence from a developmental perspective.

This paper explores the relation of the delusion of omnipotence to masochism and suggests that this fantasy constitutes a major component of the resistance so prominent in work with masochistic patients. The connections among masochism, omnipotence, negative therapeutic reaction, and clinging to pain are discussed. The classical view has been that the failure of infantile omnipotence forces the child to turn to reality. Our experience with masochistic patients suggests that it is the real failure to achieve competent interactions with others that forces the child to turn to omnipotent solutions. The distinction is made between fantasies that enhance the real capacities of the self and those aimed at denying and transforming the pain and inadequacy of the mother-child relationship. The epigenetic transformations of omnipotent fantasies through all levels of development are described. The patient's need to protect the omnipotent fantasy is discussed in relation to resistance at each phase of analysis.

Comments on termination in child, adolescent, and adult analysis.

Termination phenomena in the psychoanalytic treatment of children and adolescents demonstrate the obstacles and resistances to a mutually agreed ending, the importance of reality considerations as part of the decision to terminate, and "restoration to the path of progressive development" as the overarching criterion for the start of a termination phase. The assumption of continuity among developmental phases allows us to apply what we learn from child analysis to termination of adult cases, and this new perspective reinforces the idea that child analysis is an untapped source of insights into the analytic process.

Varieties of transference in the analysis of an adolescent.

Material from four and a half years of five times per week analysis of a 15-year-old boy is used to examine a series of transference issues, in particular the distinction between an externalizing and a differentiated transference. The initial year-and-a-half of intense anxiety and resistance to treatment is discussed in relation to this difference and the externalizing transference is viewed both as a resistance and as a step in the formation of integrated self and object representations, leading to a differentiated transference. The distinction is also of value near the end of the analysis when an attempted unilateral termination by the adolescent is conceptualized as a shift from a differentiated to an externalizing transference.