Serotonin suicidal behavior

The serotonin-boosting antidepressants are a reasonable first choice in the treatment of impulsivity and mood lability in patients with BPD. They have proved effective in the limited studies conducted thus far and are also easy to tolerate and safe in overdose. This last factor is an important consideration when treating BPD patients prone to impulsivity and at times suicidal behavior with little advance warning. When these antidepressants are used, they should be started and titrated in a similar fashion to that used in the treatment of major depression and other mood... 

The neurotransmitter serotonin (5-hydroxytryptamine [5-HT]) is widely distributed in the CNS, subsuming a variety of functions including drive satiety, mood, aggression, anxiety, and compulsive and impulsive behaviors. It may be an important neurotransmitter in psychiatric symptoms commonly associated with PTSD such as aggression, obsessive/intrusive thoughts, alcohol and substance abuse, and suicidal behavior (Friedman, 1990). Suicidal behavior is known to be associated with both childhood maltreatment and low 5-HT functioning (Van der Kolk et ah, 1991 Benkelfat,... 

An association between impulsive aggression, suicidal behavior, or both with decreased CSF levels of the serotonin metabolite 5-HIAA... 

Pandey GN, Pandey SC, Dwivedi Y, et al. Platelet serotonin-2A receptors a potential biological marker for suicidal behavior. Am J Psychiatry 1995 156 850-855. 

This neurotransmitter is contained in a few pathways, of which the midbrain raphe nuclei to the limbic-septal area (e.g., hippocampus and amygdala) is probably the most important. Serotonin abnormalities are widely reported in patients with depression, especially those with suicidal behavior, including the following ... 

Few strong biological findings demonstrating lesions in specific psychiatric disorders Example discovery of changes in serotonin receptors and metabolites in depression, schizophrenia, and suicidal behavior... 

Several studies have discussed the relationship between serum cholesterol and suicide, violence, anxiety disorders, depressive disorders, and schizophrenia [1-3]. Some of these papers suggested that low or lowering cholesterol levels could cause or worsen depressive symptoms and increase the risks of suicide and violence death. There are many reports that discussed the relationships between the lipid profiles, depression, and suicide from the viewpoints of decreased serotonergic transmission on suicide behavior [4, 5], lower serum cholesterol and serotonin levels [6, 7], serum cholesterol levels and polymorphism in the promoter region of the serotonin transporter gene for depression and suicide [8-10], low serum cholesterol and suicide risk [11, 12], and serotonergic receptor function [13, 14]. These studies supported the hypothesis that reduced cholesterol levels resulted in reduced central serotonin transmission. 

Both suicidal behavior and impulsive aggression have been associated with low levels of brain serotonergic activity [91, 92]. Engelberg suggested that a reduction in serum cholesterol may decrease brain-cell-membrane cholesterol, lower lipid microviscosity, and decrease exposure of protein serotonin receptors on the membrane surface, thus resulting in a poorer uptake of serotonin from the blood and less serotonin entry into brain cells [4]. Other reports have discussed the relationships between cholesterol, serotonin, and depression [6, 93-96]. 

Boys have more trouble than girls with teachers, parents, and classmates. Later, they are more likely to abuse alcohol and drugs (Dabbs and Morris, 1990). Aggression is often related to alcoholism. Serotonin, dopamine, epinephrine and cortisol are also involved in aggression, impulsivity, and suicidal behavior. 

In 1976, Asperg and others found reduced levels of the serotonin metabolite 5-HlAA in the cerebrospinal fluid of depressed patients who had made suicide attempts (Arch Gen Psychiatry 1976 33 1193-7). Brown and others also found a relationship between aggression, history of suicidal behavior, and 5-HIAA in cerebrospinal fluid (Psychiatry Res 1979 1 131-9.29). 

Joseph Hibbeln of the National Institutes of Health examined the levels of omega-3 fatty acids in the blood of 50 patients hospitalized after attempting suicide. Normal persons with high blood concentrations of eicosapentaenoic acid (EPA) had fewer psychological traits related to suicidal risk. He suggested "some subgroups of suicidal patients may reduce their suicidal risk with the consumption of EPA. Another study showed that dietary intake of EPA and DHA influence serotonin-related behavioral functions. 

Non-motor signs of the disorder are also treatable with symptomatic medications. The frequent mood disorder can be treated with standard antidepressants, including tricyclics (such as amitryptiline) or serotonin reuptake inhibitors (SSRIs, such as fluoxetine or sertraline). This treatment is not without risks in these patients, as it may trigger manic episodes or may even precipitate suicide. Anxiety responds to benzodiazepines, as well as to effective treatment of depression. Long-acting benzodiazepines are favored over short-acting ones because of the lesser abuse potential. Some of the behavioral abnormalities may respond to treatment with the neuroleptics as well. The use of atypical neuroleptics, such as clozapine is preferred over the typical neuroleptics as they may help to control dyskinesias with relatively few extrapyramidal side-effects (Ch. 54). 

Imipramine (Tofranil) [Antidepressant/TCA] WARNING Close observation for suicidal thinking or unusual changes in behavior Uses Depres-sion, enuresis, panic attack, chronic pain Action TCA t CNS synaptic serotonin or norepinephrine Dose Adults. Hospitalized Initial 100 mg/24 h PO in doses T over several wk 300 mg/d max Output Maint 50-150 mg PO hs, 300 mg/24 h max Peds. Antidepressant 1.5-5 mg/kg/24 h daUy-qid Enuresis >6 y 10-25 mg PO qhs T by 10-25 mg at 1-2-wk int vals (max 50 mg for 6-12 y, 75 mg for >12 y) Rx for 2-3 mo, then tap Caution [D, /-] Contra Use w/ MAOIs, NAG, acute recovery from MI, PRG, CHF, angina, CVD, arrhythmias Disp Tabs, caps SE CV Sxs, dizziness, xerostomia, discolored urine Interactions t Effects W/ amiodarone, anticholinergics, BBs, cimetidine, diltiazem, Li, OCPs, quinidine, phenothiazines, ritonavir, verapamil, EtOH, evening primrose oil t effects OF CNS depressants, hypoglycemics, warfarin T risk of serotonin synd W/MAOIs 4-... 

Serotonin Reexperiencing, avoidance and psychic numbing, hyperarousal, mood, impulsive-compulsive behaviors, aggression, suicide, rage, chemical abuse and/or dependency... 

The clinical implications of such data point to a relationship between abnormalities in the central serotonin system and self-injurious behavior. These findings have led to an interest in developing specific drugs that alter 5-HT activity to treat suicidality, impulsivity, and aggressivity independent of any specific psychiatric disorder. Central serotonin function can be enhanced by agents such as lithium and various serotonin reuptake inhibitors. Recent studies have found that the use of such agents is associated with reductions in the likelihood of suicide attempts and completions in both patients with major depression and those with cluster... 

Studies of depressed patients have sometimes shown an alteration in monoamine function. For example, some studies have found evidence of alteration in serotonin receptor numbers (5-HT1A and 5-HT2c) or norepinephrine (k2) receptors in depressed and suicidal patients, but these findings have not been consistent. A reduction in the primary serotonin metabolite 5-hydroxyindoleacetic acid in the cerebrospinal fluid is associated with violent and impulsive behavior, including violent suicide attempts. However, this finding is not specific to major depression and is associated more generally with violent and impulsive behavior. 

The capacity for SSRIs to induce akathisia—and for akathisia to cause suicidality, aggression, and a worsening mental condition—is also recognized in the DSM-IV and the DSM-IV-TR in the section dealing with neuroleptic-induced akathisia. The DSM-IV-TR observes, Akathisia may be associated with dysphoria, irritability, aggression, or suicide attempts. It also mentions worsening of psychotic symptoms or behavioral dyscontrol. It then states, Serotonin-specific reuptake inhibitor antidepressant medications may produce akathisia that appears identical in phenomenology and treatment response to Neuroleptic-Induced Acute Akathisia (p. 801). 

Serotonin deficiency is related to a broad array of emotional and behavioral problems, ranging from depression, premenstrual syndrome, anxiety, alcoholism, insomnia, violence, aggression, suicide, and compulsive gambling. 

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