Cognitive-behavioural therapy in medication-treated adults with attention-deficit/hyperactivity disorder and co-morbid psychopathology:a randomized controlled trial using multi-level analysis

Background. Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by high rates of co-morbid psychopathology. Randomized controlled trials of multimodal interventions, combining pharmacological and psychological treatments, have shown a robust treatment effect for ADHD symptoms but outcomes for co-morbid symptoms have been mixed. This may be accounted for by the type of intervention selected and/or by methodological problems including lack of follow-up and low power. The current study addressed these limitations in a parallel-group randomized controlled trial conducted in Iceland.  Method. A total of 95 adult ADHD patients who were already being treated with medication (MED) were randomly assigned to receive treatment as usual (TAU/MED) or 15 sessions of cognitive-behavioural therapy (CBT/MED) using the R&R2ADHD intervention which employs both group and individual modalities. Primary measures of ADHD symptoms and severity of illness, and secondary measures of anxiety, depression and quality of life were given at baseline, end of treatment and 3-month follow-up. Primary outcomes were rated by clinicians blind to treatment condition assignment.  Results. CBT/MED showed overall (combined outcome at end of treatment and 3-month follow-up) significantly greater reduction in primary outcomes for clinician-rated and self-rated ADHD symptoms. Treatment effect of primary outcomes was maintained at follow-up, which suggests robust and lasting findings. In contrast to the primary outcomes, the secondary outcomes showed significant improvement over time.  Conclusions. The study provides evidence for the effectiveness of R&R2ADHD and demonstrates that there are differential effects over time for ADHD symptoms versus co-morbid problems, the latter taking longer to show positive effects

Bericht \ufcber die Leistungen im Gebiete der Zoologie w\ue4hrend des Jahres 1838

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Acid sphingomyelinase-ceramide system mediates effects of antidepressant drugs

Major depression is a highly prevalent severe mood disorder that is treated with antidepressants. The molecular targets of antidepressants require definition. We investigated the role of the acid sphingomyelinase (Asm)-ceramide system as a target for antidepressants. Therapeutic concentrations of the antidepressants amitriptyline and fluoxetine reduced Asm activity and ceramide concentrations in the hippocampus, increased neuronal proliferation, maturation and survival and improved behavior in mouse models of stress-induced depression. Genetic Asm deficiency abrogated these effects. Mice overexpressing Asm, heterozygous for acid ceramidase, treated with blockers of ceramide metabolism or directly injected with C16 ceramide in the hippocampus had higher ceramide concentrations and lower rates of neuronal proliferation, maturation and survival compared with controls and showed depression-like behavior even in the absence of stress. The decrease of ceramide abundance achieved by antidepressant-mediated inhibition of Asm normalized these effects. Lowering ceramide abundance may thus be a central goal for the future development of antidepressants

The “outer dimensions”: impulsivity, anger/aggressiveness, activation

The “outer” SVARAD dimensions, impulsivity, anger/aggressiveness, and activation, represent trans-diagnostic psychological and behavioural domains that span traditional categorical boundaries. At the neurobiological level, the fronto-limbic and the fronto-cerebellar circuitry, as well as molecular pathways involving dopamine, serotonin, testosterone, and inflammatory mediators, play a crucial role in mediating the biological underpinnings of these psychopathological dimensions. From a clinical perspective, as the combination of clusters of symptoms differs from patient to patient and gives rise to a wide variety of clinical pictures even among subjects with the same diagnosis, it is important that the clinical features related to impulsivity, anger, aggressiveness, and activation are specifically and multiparametrically investigated and treated. The aim of the present chapter is to discuss the psychopathological aspects, the neurobiological underpinnings, and the clinical implications related to the “outer dimensions” in clinical psychiatry