D. Marazziti - Vol. 10, December 2004, Issue 4
Testo Bibliografia Summary Indice
Serotonina e psicopatologia
Serotonin and psychopathology
Serotonin, a neurotransmitter discovered about 70 years ago, is involved in several physiological processes within the central nervous system. Its derangement underlies symptoms involved in many psychopathological dimensions. Improved imaging, neurophysiological and neurochemical techniques allowed for better studying its role in various psychiatric disorders. Brain imaging studies showed decreased serotonergic transmission in the median raphe nucleus and its prefrontal projections in depressed patients, metabolic studies showed decreased plasma availability of its precursor in depression, post-mortem studies showed up-regulated brain 5-HT2 and 5-HT1A receptors and decreased serotonin transporter (5-HTT) levels in depressed patients, as well as autoreceptor down-regulation after chronic selective serotonin reuptake inhibitor (SSRI) treatment, chemical assays revealed decreased cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA), especially in relation to aggressive behavior directed to oneself or others, binding studies showed 5-HTT down-regulation in platelets of depressed patients which is stronger in women and in patients at higher risk for suicide, finally, neuroendocrine studies are consistent with impaired serotonin transmission in depression. In obsessive-compulsive disorder (OCD), reduced 5-HTT function correlates with symptom severity and SSRI responsiveness. Genetic studies yielded controversial results as for the 5-HTT in this disorder, but showed functional polymorphism for both postsynaptic 5-HT2A receptor and terminal 5-HT1D autoreceptor. Studies of second messengers seem to indicate an imbalance between cyclic AMP and phosphoinoside-related intracellular processes towards the latter and SSRIs appear to interfere with the phosphoinositide cycle, upregulating neurotrophic factors involved in brain plasticity, such BDNF and CREB, which are the target of the action of the 5-HT2C receptor. Neuroendocrine challenge studies also show blunted ACTH response to CRH in OCD patients and this is matched by increased CSF levels of ACTH in both patients with OCD and Tourette disorder, a disorder of the OCD spectrum, which is also characterized by decreased post-mortem serotonin and 5-HIAA brain levels. Various disorders of the OCD spectrum show reduced platelet 5-HTT levels. In patients with panic disorder, neuroendocrine and platelet serotonin reuptake studies yielded inconsistent results; a positron emission tomography (PET) study showed short 5-HTT gene promoter variant polymorphism in subjects with increased amygdalar sensitivity and higher trait and state anxiety levels. In social phobia (SPh), neuroendocrine challenge studies did not differentiate index subjects from controls except for two studies showing increased plasma cortisol response to fenfluramine, but abnormal activation of the amygdala was shown after exposure to fearful stimulation in subjects with SPh, which normalized after SSRI treatment. In eating disorders and psychoses, changes in serotonergic transmission are controversial and could be nonspecific.