[Adult attention deficit/hyperactivity disorder, associated symptoms and comorbid psychiatric disorders: diagnosis and pharmacological treatment]. / Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung bei Erwachsenen mit assoziierter Symptomatik und komorbiden psychiatrischen Erkrankungen: Diagnostik und medikamentöse Behandlung.

Adult attention deficit/hyperactivity disorder (ADHD) is characterised by inattention and/or hyperactivity and impulsivity and is a frequent psychiatric disorder with childhood onset. In addition to core symptoms, patients often experience associated symptoms like emotional dysregulation or low self-esteem and suffer from comorbid disorders, particularly depressive episodes, substance abuse, anxiety or sleep disorders. It is recommended to include associated symptoms and comorbid psychiatric disorders in the diagnostic set-up and in the treatment plan. Comorbid psychiatric disorders should be addressed with disorder-specific therapies while associated symptoms also often improve with treatment of the ADHD core symptoms. The most impairing psychiatric disorder should be treated first. This review presents recommendations for differential diagnosis and treatment of adult ADHD with associated symptoms and comorbid psychiatric disorders with respect to internationally published guidelines, clinical trials and expert opinions.

Intranasal insulin-like growth factor I (IGF-I) as a plausible future treatment of depression.

Depression remains a highly prevalent and mostly recurrent disorder causing an increased need to optimize and broaden the current therapy options. An enormous body of evidence links the regulation of specific neurotrophic proteins, like the brain-derived neurotrophic factor (BDNF), to depression and it may be assumed that the behavioral effects of antidepressants require functional BDNF signaling in the brain. Another neurotrophin, insulin-like growth factor-I (IGF-I), also produces antidepressant-like behavioral effects. Data have shown that BDNF plus IGF-I are more effective than either neurotrophin alone in activating neurotrophic cascades and promoting survival of hippocampal neurons. In fact, it has been suggested that the increase in hippocampal BDNF following antidepressant treatment or physical exercise in animal models is IGF-I-dependent and that antidepressant treatment increases IGF-I in human cerebrospinal fluid (CSF). Thus, BDNF and IGF-I seem to act synergistically in the same cascade of transmission and neuroplasticity. In order to avoid the pitfalls of systemic application (e.g. possible peripheral side effects) while directly targeting central nervous circuitries, the clinical intranasal administration of IGF-I appears to be a plausible and promising treatment option of depression.

Insulin secretion and sensitivity after single-dose amisulpride, olanzapine or placebo in young male subjects: double blind, cross-over glucose clamp study.

INTRODUCTION: Increased risks of weight gain and diabetes mellitus have been reported for schizophrenic patients under long-term treatment with several atypical antipsychotic drugs including olanzapine. Among other antipsychotic drugs, treatment with the selective dopamine D2 and D3 receptor antagonist amisulpride has been implicated with a lower risk for metabolic complications. PATIENTS AND METHODS: In this study we compared the acute, non-adiposity related effects of a single dose of olanzapine, amisulpride and placebo on insulin sensitivity and secretion in 10 healthy subjects in a randomised, double blind cross-over design. Subjects underwent euglycemic-hyperinsulinemic and hyperglycemic clamp tests using an automated clamp device. C-peptide and pro-insulin levels were determined using highly specific immuno-assays. RESULTS: Insulin sensitivity was not significantly different between both verum medications and placebo. However, C-peptide secretion during hyperglycemic clamp was significantly higher after administration of amisulpride than after olanzapine or placebo. This was true both for the early phase and for the second phase of insulin secretion (C-peptide at 0, 5,10 and 30 min: amisulpride 1.49±0.49; 4.22±1.45; 3.19±1.22; 5.33±1.85; olanzapine 1.35±0.47; 3.84±1.37; 2.72±0.91; 4.28±1.96; placebo 1.72±0.82; 3.59±1.19; 2.71±1.02; 4.54±1.42 ng/mL, mean±SD; ANOVA p=0.043). Pro-insulin levels did not differ significantly between groups. DISCUSSION: A low dose of the D2/D3 antagonist amisulpride, but not olanzapine appears to acutely increase pancreatic insulin secretion in healthy controls. Stimulation of ß-cells could be a protective factor against the development of diabetes mellitus.

The differential effect of risperidone and olanzapine on insulin sensitivity after 3 weeks of treatment: a HOMA pilot study.

BACKGROUND AND METHODS: Patients with an acute psychotic episode underwent HOMA testing for insulin sensitivity (IS) prior to and after 3 weeks of treatment with olanzapine (n = 7) or risperidone (n = 7). RESULTS AND DISCUSSION: The HOMA-IS index was reduced in the olanzapine group, but significantly increased in patients treated with risperidone. There was a significant "time × medication" interaction (p = 0.03). The BMI significantly increased as a result of both treatments. IS can be acutely ameliorated by antipsychotic treatment with risperidone despite weight increase. CONCLUSIONS: Compared to risperidone, the IS is impaired after a 3-week treatment with olanzapine. Already short-term antipsychotic treatment may have eff ects on insulin sensitivity.

[Epigenetic mechanisms in major depression]. / Epigenetische Mechanismen der Depression.

The term epigenetics describes mechanisms that can change the function of genes in the absence of an alteration of the actual DNA sequence. Among others, histone protein modifications (methylation, acetylation and phosphorylation) and DNA methylation constitute epigenetic mechanisms. Histone methylation and histone deacetylation in promoter regions of neurotrophic factors that have been associated with depression lead to their reduced expression. The methylation of DNA in promoter regions of genes coding for receptors and neurotrophic factors also results in their reduced expression, as was revealed for depressive disorders. Preclinical studies have shown that maternal care has a crucial influence on the reactivity of the hypothalamic-pituitary-adrenocortical axis of the offspring due to epigenetic mechanisms. These are acquired modifications that can be partially reversed by drug treatment (antidepressants).

[The role of the glutamatergic system in pathophysiology and pharmacotherapy for depression: preclinical and clinical data]. / Die Bedeutung des glutamatergen Systems für Pathophysiologie und Pharmakotherapie der Depression: präklinische und klinische Daten.

An increasing significance has been attributed to the glutamatergic system in the pathophysiology of affective disorders. Glutamate is the most important excitatory neurotransmitter in the central nervous system. Glia cells are crucial regulators of the glutamatergic metabolism. Several studies have reported a dysfunction or reduced number of glia cells in patients suffering from depression. This could result in hyperfunctioning of the glutamatergic system leading to a toxic accumulation of glutamate. Commonly used antidepressants influence the glutamate metabolism and antiglutamatergic substances [e. g., riluzol] and NMDA-receptor antagonists [e. g., ketamine] have shown antidepressant properties in mostly preclinical and some clinical trials. Further substances are currently being investigated. This review provides an insight into the newest developments in this field.

[Methylphenidate. Therapy option for adults with ADHD and comorbid substance use disorder?]. / Methylphenidat. Therapieoption bei ADHS und Suchterkrankung im Erwachsenenalter?

Attention-deficit/hyperactivity disorder (ADHD) in adults is often associated with a comorbid substance use disorder (SUD). To date, no treatment algorithms are available. The question of whether the administration of methylphenidate (MPH) is justified in the treatment of adult patients with ADHD and comorbid SUD still remains unclear. While animal studies indicate an addictive potential of intravenous application of the drug, controlled oral treatment with MPH does not seem to carry the potential for abuse in humans. It remains controversial whether MPH treatment of ADHD during childhood protects against the development of SUD during adulthood. Although data remain inconsistent, a small number of studies and our own clinical observations of ADHD patients with SUD treated with MPH support a reduction not only of ADHD-related symptoms, but also of craving and substance abuse. The treatment of the adult ADHD with comorbid SUD with MPH should be conducted after a risk-benefit assessment, taking into consideration the abused substances, the motivation to abstinence and the quality of the physician-patient relationship; it should be evaluated critically, monitored closely and accompanied by treatment of the SUD and specific psychotherapy/psychoeducation.