ABSTRACT
People with developmental disabilities are at considerable risk for the development of comorbid psychiatric conditions. Psychopharmacological treatments may have a crucial role in a multidisciplinary and multimodal approach to the management of psychopathology in this population. Psychiatric illnesses that are particularly amenable include mood disorders, anxiety disorders, schizophrenia, and attention deficit hyperactivity disorders (ADHDs) and antidepressants, mood stabilisers, anxiolytics, antipsychotics, and stimulants should be considered, respectively. ADHD may also respond to alpha(2)-agonists. Psychotropic agents such as beta-antagonists can target aggressive, self injurious, and stereotypical behaviours and opioid antagonists may be helpful in treating self injurious behaviour and stereotypy. Selective serotonin reuptake inhibitors, newer anticonvulsants, and atypical neuroleptics are preferred when treating psychiatric disorders among people with developmental disabilities. This paper will review the major studies of pharmacological treatment of mental illness in individuals with developmental disabilities.
Subject(s)
Developmental Disabilities/psychology , Mental Disorders/drug therapy , Adrenergic alpha-Agonists , Adrenergic beta-Antagonists/therapeutic use , Anti-Anxiety Agents/therapeutic use , Antidepressive Agents/therapeutic use , Antipsychotic Agents/therapeutic use , Central Nervous System Stimulants/therapeutic use , Child , Clonidine/therapeutic use , Forecasting , Humans , Mental Disorders/complications , Narcotic Antagonists/therapeutic use , Practice Guidelines as TopicABSTRACT
1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) primes NB4 cells for 12-O-tetradecanoylphorbol-13-acetate-induced monocytic differentiation in a dose- and sequence-dependent fashion. Experiments utilizing 1,25-(OH)2D3 analogues and kinase/phosphatase inhibitors suggested that tyrosine kinase and serine/threonine phosphorylation cascades, rather than vitamin D3 receptor-mediated signals, were involved in 1,25-(OH)2D3 action. Here we show that NB4 cells express the alpha and delta (but not the beta, epsilon, and theta) isoforms of protein kinase C (PKC). Both authentic 1, 25-(OH)2D3 and the nongenomic analogue 1alpha,25-dihydroxyprevitamin D3 (HF) increased expression of PKCalpha and PKCdelta. PKCalpha and PKCdelta were translocated to the nucleus of the cell in response to 1,25-(OH)2D3 or HF. The effects of HF were attenuated by the nongenomic antagonist 1beta,25-dihydroxyvitamin D3, suggesting that changes in PKC expression are mediated by a nongenomic signaling pathway. Consistent with the involvement of serine, threonine, and tyrosine phosphorylation cascades mediating 1,25-(OH)2D3 action, enhanced phosphorylation of a variety of cellular proteins at serine and threonine residues and the specific enhanced phosphotyrosyl content of a 33-kDa protein (vdrp33) were observed immediately after 1,25-(OH)2D3 addition. We propose that 1,25-(OH)2D3 primes NB4 cells for 12-O-tetradecanoylphorbol-13-acetate-induced monocytic differentiation by increasing the expression of specific PKC isoforms and inducing the specific phosphorylation of key protein signaling intermediates.