[Treatment of emotion regulation problems in people with neurofibromatosis type 1]. / Behandeling van emotieregulatieproblemen bij mensen met neurofibromatose type 1.

Individuals with the genetic disorder neurofibromatosis type 1 (NF1) are typically diagnosed in a medical hospital setting strongly relying on the presence of well-defined physical symptoms such as neurofibromas or pigmentary spots (known as café-au-lait spots). In mental health care settings, however, aside from a few highly specialized centres, the diagnosis and treatment of individuals with NF1 receives little attention, while the need for psychological treatment is increasingly identified, both in clinical practice and in the scientific literature. Occasional referrals of individuals with NF1 to the mental health services are often only targeted at psychological assessment. Subsequent treatment, however, is usually lacking. We describe two individuals with NF1 for whom by means of specialized clinical neuropsychological assessment, participation in a tailored dialectical behavior therapy (DBT) skills training was indicated. We exposit how they were able to develop their skills and how they themselves and their significant others experienced the treatment.

Perceived Criticism in Relation to the Dialectical Behaviour Therapy Network Training in a Residential Program: A Pre-Post Study

Perceived Criticism is a transdiagnostic construct that captures the patients’ perception of criticism. PC seems to be a reliable predictor of negative clinical outcomes concerning recurrence of symptoms or relapse in a broad range of stress-related psychiatric disorders and is thought to be related to underlying stress-related psychobiological vulnerabilities. Dialectical Behavior Therapy (DBT) is a treatment targeting these stress-related psychobiological vulnerabilities. In this pilot study we focus on the possible change in Perceived Criticism due to a (residential) DBT network training. This study follows a pre-post design where PC is recorded in 33 patients (mean age 25 years) and 61 relatives during 8 group sessions of a DBT network training, as part of a residential DBT program. The degree of perceived criticism is systematically assessed using the Perceived Criticism Measure, a two item self-report questionnaire that assesses mutual (perceived) criticism from patients and network members. Overall scores of the perceived criticism measure decrease significantly for both patients and relatives after following the DBT network training. More specific, item scores of both patients and relatives concerning how critical they are towards the other and how critical they thought the other was of them also decreased significantly after following the DBT network training. Findings suggest that a DBT network training as part of a residential DBT program may be instrumental in decreasing levels of perceived criticism. We recommend further exploration of Perceived Criticism as a possible moderator in effect size studies in randomized controlled clinical trials on DBT and in more fundamental research on the putative mechanisms of behavioural change such as improved perspective taking, and the evaluation of social cues (AU)

Allopregnanolone and mood disorders.

UNLABELLED: Certain women experience negative mood symptoms during the menstrual cycle and progesterone addition in estrogen treatments. In women with PMDD increased negative mood symptoms related to allopregnanolone increase during the luteal phase of ovulatory menstrual cycles. In anovulatory cycles no symptom or sex steroid increase occurs. This is unexpected as positive modulators of the GABA-A receptor are generally increasing mood. This paradoxical effect has brought forward a hypothesis that the symptoms are provoked by allopregnanolone the GABA-A receptor system. GABA-A is the major inhibitory system in the brain. Positive modulators of the GABA-A receptor include the progesterone metabolites allopregnanolone and pregnanolone, benzodiazepines, barbiturates, and alcohol. GABA-A receptor modulators are known, in low concentrations to induce adverse, anxiogenic effects whereas in higher concentrations show beneficial, calming properties. Positive GABA-A receptor modulators induce strong paradoxical effects e.g. negative mood in 3-8% of those exposed, while up to 25% have moderate symptoms thus similar as the prevalence of PMDD, 3-8% among women in fertile ages, and up to 25% have moderate symptoms of premenstrual syndrome (PMS). The mechanism behind paradoxical reaction might be similar among them who react on positive GABA-A receptor modulators and in women with PMDD. In women the severity of these mood symptoms are related to the allopregnanolone serum concentrations in an inverted U-shaped curve. Negative mood symptoms occur when the serum concentration of allopregnanolone is similar to endogenous luteal phase levels, while low and high concentrations have less effect on mood. Low to moderate progesterone/allopregnanolone concentrations in women increases the activity in the amygdala (measured with fMRI) similar to the changes seen during anxiety reactions. Higher concentrations give decreased amygdala activity similar as seen during benzodiazepine treatment with calming anxiolytic effects. Patients with PMDD show decreased sensitivity in GABA-A receptor sensitivity to diazepam and pregnanolone while increased sensitivity to allopregnanolone. This agrees with findings in animals showing a relation between changes in alpha4 and delta subunits of the GABA-A receptor and anxiogenic effects of allopregnanolone. CONCLUSION: These findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor.

Gonadal hormone regulation of the emotion circuitry in humans.

Gonadal hormones are known to influence the regulation of emotional responses and affective states. Whereas fluctuations in progesterone and estradiol are associated with increased vulnerability for mood disorders, testosterone is mainly associated with social dominance, aggressive, and antisocial behavior. Here, we review recent functional neuroimaging studies that have started to elucidate how these hormones modulate the neural circuitry that is important for emotion regulation, which includes the amygdala and the medial prefrontal (mPFC) and orbitofrontal cortex (OFC). The amygdala is thought to generate emotional responses, and the prefrontal brain regions to regulate those responses. Overall, studies that have investigated women during different phases of the menstrual cycle suggest that progesterone and estradiol may have opposing actions on the amygdala and prefrontal cortex. In addition, the influence of exogenous progesterone appears to be dose-dependent. Endogenous testosterone concentrations are generally positively correlated to amygdala and OFC responses, and exogenous testosterone increases amygdala reactivity. Whereas the administration of progesterone increases amygdala reactivity and its connectivity with the mPFC, testosterone administration increases amygdala reactivity but decreases its connectivity with the OFC. We propose that this opposing influence on amygdala-prefrontal coupling may contribute to the divergent effects of progesterone and testosterone on emotion regulation and behavioral inhibition, respectively, which may promote the differential vulnerability to various psychiatric disorders between women and men. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.

Paradoxical effects of GABA-A modulators may explain sex steroid induced negative mood symptoms in some persons.

Some women have negative mood symptoms, caused by progestagens in hormonal contraceptives or sequential hormone therapy or by progesterone in the luteal phase of the menstrual cycle, which may be attributed to metabolites acting on the GABA-A receptor. The GABA system is the major inhibitory system in the adult CNS and most positive modulators of the GABA-A receptor (benzodiazepines, barbiturates, alcohol, GABA steroids), induce inhibitory (e.g. anesthetic, sedative, anticonvulsant, anxiolytic) effects. However, some individuals have adverse effects (seizures, increased pain, anxiety, irritability, aggression) upon exposure. Positive GABA-A receptor modulators induce strong paradoxical effects including negative mood in 3%-8% of those exposed, while up to 25% have moderate symptoms. The effect is biphasic: low concentrations induce an adverse anxiogenic effect while higher concentrations decrease this effect and show inhibitory, calming properties. The prevalence of premenstrual dysphoric disorder (PMDD) is also 3%-8% among women in fertile ages, and up to 25% have more moderate symptoms of premenstrual syndrome (PMS). Patients with PMDD have severe luteal phase-related symptoms and show changes in GABA-A receptor sensitivity and GABA concentrations. Findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor, which may be explained by one or more of three hypotheses regarding the paradoxical effect of GABA steroids on behavior: (1) under certain conditions, such as puberty, the relative fraction of certain GABA-A receptor subtypes may be altered, and at those subtypes the GABA steroids may act as negative modulators in contrast to their usual role as positive modulators; (2) in certain brain areas of vulnerable women the transmembrane Cl(-) gradient may be altered by factors such as estrogens that favor excitability; (3) inhibition of inhibitory neurons may promote disinhibition, and hence excitability. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.