Necessity of Hippocampal Neurogenesis for the Therapeutic Action of Antidepressants in Adult Nonhuman Primates

Rodent studies show that neurogenesis is necessary for mediating the salutary effects of antidepressants. Nonhuman primate (NHP) studies may bridge important rodent findings to the clinical realm since NHP-depression shares significant homology with human depression and kinetics of primate neurogenesis differ from those in rodents. After demonstrating that antidepressants can stimulate neurogenesis in NHPs, our present study examines whether neurogenesis is required for antidepressant efficacy in NHPs. MATERIALS/METHODOLOGY: Adult female bonnets were randomized to three social pens (N = 6 each). Pen-1 subjects were exposed to control-conditions for 15 weeks with half receiving the antidepressant fluoxetine and the rest receiving saline-placebo. Pen-2 subjects were exposed to 15 weeks of separation-stress with half receiving fluoxetine and half receiving placebo. Pen-3 subjects 2 weeks of irradiation (N = 4) or sham-irradiation (N = 2) and then exposed to 15 weeks of stress and fluoxetine. Dependent measures were weekly behavioral observations and postmortem neurogenesis levels.Exposing NHPs to repeated separation stress resulted in depression-like behaviors (anhedonia and subordinance) accompanied by reduced hippocampal neurogenesis. Treatment with fluoxetine stimulated neurogenesis and prevented the emergence of depression-like behaviors. Ablation of neurogenesis with irradiation abolished the therapeutic effects of fluoxetine. Non-stressed controls had normative behaviors although the fluoxetine-treated controls had higher neurogenesis rates. Across all groups, depression-like behaviors were associated with decreased rates of neurogenesis but this inverse correlation was only significant for new neurons in the anterior dentate gyrus that were at the threshold of completing maturation.We provide evidence that induction of neurogenesis is integral to the therapeutic effects of fluoxetine in NHPs. Given the similarity between monkeys and humans, hippocampal neurogenesis likely plays a similar role in the treatment of clinical depression. Future studies will examine several outstanding questions such as whether neuro-suppression is sufficient for producing depression and whether therapeutic neuroplastic effects of fluoxetine are specific to antidepressants

The age of onset of anxiety disorders

Book cover Age of Onset of Mental Disorders pp 125–147Cite as The Age of Onset of Anxiety Disorders Jeroen S. Legerstee, Bram Dierckx, Elisabeth M. W. J. Utens, Frank C. Verhulst, Carola Zieldorff, Gwen C. Dieleman & Jasmijn M. de Lijster Chapter First Online: 12 November 2018 1043 Accesses Abstract Anxiety disorders are highly prevalent and debilitating psychiatric conditions, which often remain unrecognised and untreated. However, left untreated, anxiety disorders often persist and can contribute to the development of other psychiatric disorders. Therefore, early detection and subsequent intervention are important. Information on the age of onset (AOO) of anxiety disorders could be informative for the timing of prevention strategies. The aim of this chapter is to review and quantitatively synthesise previous findings on the AOO of anxiety disorders. We extended data of a previous meta-analysis of our research group (de Lijster et al. 2017) with a literature search of studies published between October 2014 and June 2017. Anxiety disorders in general were found to have their mean onset at 21 years, which is earlier than the average onset of mood disorders and substance use disorders. However, the age period in which anxiety disorders develops is relatively broad. Separation anxiety disorder, specific phobia and social phobia have their onset in childhood and adolescence, whereas agoraphobia, obsessive–compulsive disorder, post-traumatic stress disorder and panic disorder have their onset in early adulthood. Generalised anxiety disorder had the latest mean onset at almost 35 years

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_Objective:_ The objective was to estimate the age of onset (AOO) for all anxiety disorders and for specific subtypes. Gender differences in the AOO of anxiety disorders were examined, as were the influence of study characteristics on reported AOOs. _Methods:_ Seven electronic databases were searched up to October 2014, with keywords representing anxiety disorder subtypes, AOO, and study design. The inclusion criteria were studies using a general population sample that provided data on the AOO for all anxiety disorders, or specific anxiety disorders, according to DSM-III-R, DSM-IV, or ICD-10 criteria. _Results:_ There were 1028 titles examined, which yielded 24 studies meeting the inclusion criteria. Eight studies reported the AOO and gender. Meta-analysis found a mean AOO of all anxiety disorders of 21.3 years (95% CI 17.46 to 25.07). Separation anxiety disorder, specific phobia, and social phobia had their mean onset before the age of 15 years, whereas the AOO of agoraphobia, obsessive-compulsive disorder, posttraumatic stress disorder, panic disorder, and generalized anxiety disorder began, on average, between 21.1 and 34.9 years. Meta-analysis revealed no difference in the AOO between genders. A prospective s