Martin L. Korn

Denosologization of biological psychiatry or the specificity of 5-HT disturbances in psychiatric disorders

5-Hydroxytryptamine (5-HT) disorders have been reported to occur in a variety of psychiatric disorders. The situation has been called chaotic, the disturbances non-specific. We reject this viewpoint. 5-HT disturbances are non-specific only from a nosological/categorical viewpoint; they seem rather specific from a functional/dimensional point of view, correlating as they do with particular psychopathological dimensions, i.e. aggression-, anxiety- and possibly mood-disregulation, across diagnosis. The evolution of 5-HT research in psychiatry illustrates the importance of what we have called the functional approach, implying dissection of a given psychopathological syndrome in its component parts, i.e., the psychological dysfunctions, and searching for correlations between biological and psychological dysfunctions. The rigid preoccupation of biological psychiatry with the search for markers of disease entities has hampered progress. The functional approach should be incorporated in biological psychiatry, not as an alternative for the nosological approach but as its complement.

Interrelationships among anxiety, aggression, impulsivity, and mood: a serotonergically linked cluster?

Serotonin abnormalities appear to be related to a variety of psychopathological dimensions such as anxiety, depressed mood, impulsivity, and aggression dysregulation. We hypothesized that the psychopathological dimensions related to serotonin would be significantly intercorrelated since they seem to have a common biological basis. Sixty psychiatric inpatients were examined on a series of psychometric tests measuring suicidality, violence potential, impulsivity, depressive mood, and anxiety. The scores on all of these measures tended to be significantly correlated with one another. These findings support the additional hypothesis that biological markers may be more closely related to basic psychological dimensions than to nosological categories.

Is there a relation between the seriousness of suicidal intent and the lethality of the suicide attempt

The relation between the strength of an individuals intent to commit suicide and the nature and seriousness (lethality) of any suicide attempt has been a controversial one. Some studies suggest a positive correlation, while others report no connection. The present investigation included 60 patients, who were studied shortly after they had been admitted to a medical service after a suicide attempt. Measures of depression, impulsivity, suicidal intent, seriousness of the attempt, and efforts to prevent intervention were obtained. Results reveal that both depression and impulsivity correlate positively with the strength of the intent to commit suicide, but there appears to be almost no correlation in this population between measures of intent and seriousness of the attempt.

Serotonin receptor sensitivity and aggression

This study investigated the relationship between increased serotonin (5-hydroxytryptamine, 5HT) receptor sensitivity and human aggression. A low oral dose of meta-chlorophenylpiperazine (MCPP), a postsynaptic 5HT receptor agonist, was administered in a placebo-controlled design to depressed (n = 22) and panic disorder (n = 20) patients classified with or without signs of outwardly directed aggression, patients with a history of suicide attempts (inwardly directed aggression) (n = 11), and normal controls (n = 19). Hormones under 5HT control were measured at 30-min intervals. Results were as follows: (1) MCPP did not induce or reduce anger, (2) patients with outwardly directed aggression did not have significantly greater MCPP-induced cortisol or prolactin release than did patients without signs of outwardly directed aggression, (3) patients with a history of suicide attempts did not have significantly greater MCPP-induced cortisol or prolactin release than did normal controls, and (4) MCPP-induced hormone release was unrelated to measures of aggression.

Headache and Cortisol Responses to M-Chlorophenylpiperazine are Highly Correlated

The serotonin receptor agonist m-chlorophenylpiperazine (m-CPP) stimulates the release of cortisol and prolactin, and induces migraine-like headaches. We have studied the neuroendocrine and headache responses to m-CPP in 8 subjects with migraine and I0 normal subjects. Each subject underwent two challenge tests, one with 0.25 mg/kg PO of m-CPP and the other with placebo, administered in a double-blind crossover format. Serial measurements of serum cortisol, prolactin, and m-CPP levels were made at 30-min intervals for 210 min following ingestion of the medication. The incidence and severity of headache was assessed by a structured telephone interview after each test. We confirmed that m-CPP stimulates the release of cortisol and prolactin, and may induce headache, in both migraine subjects and normal controls. The cortisol response as well as ratings of headache severity and duration directly correlated with plasma levels of m-CPP. There were highly significant associations between the cortisol response and both headache severity and duration, independent of m-CPP plasma levels. We did not find statistically significant differences between the migraine and normal subjects in terms of their neuroendocrine or headache responses to m-CPP.

The Suicide and Aggression Survey: a semistructured instrument for the measurement of suicidality and aggression.

Despite the rising concern with the increasing rate of violent and suicidal behaviors in this country and others, we remain relatively limited in our ability to rigorously define, classify, and measure these behaviors. In addition to our previous work in developing self-rating scales assessing aspects of aggressive behaviors, we have developed the Suicide and Aggression Survey (SAS), a new, comprehensive, semistructured interview and research tool, for the purpose of comprehensively evaluating and understanding the multiple constituents of these behaviors, and for assisting in predicting which individuals might be at high risk for suicide or violence. The present report describes the need for such an instrument and the theoretical models that have guided us in constructing it; one of these is a sequential description of the major classes of variables related to aggression and the other is a two-stage model of countervailing forces. Preliminary reliability data and a description of the structure of the interview are included.

Suicide and violence associated with panic attacks

Several studies have indicated that patients with panic attacks have a higher rate of suicide attempts as well as deaths from suicide. Additionally, several investigators have presented case reports of individuals manifesting suicidal and violent behaviors directly and temporally associated with panic attacks. We report on four additional cases and suggest that these findings may explain, in part, the increased rate of suicidal behavior among patients with panic attacks found by some investigators. Furthermore, these case reports offer preliminary evidence that the relationship between violent behavior and the panic state may be clinically significant and deserving of further elucidation.

Serotonin in Depression and Anxiety

Data on 5HT in depression are disparate in nature and difficult to compress into a unifying theory. We summarize our own belief that the specificity of 5HT dysfunctions may be better related to certain psychopathological phenomena rather than to depression per se. Data linking 5HT dysfunction, and in particular postsynaptic 5HT receptor hypersensitivity, to panic disorder are presented and preliminary results on 5HT and suicidality are discussed. As other data have shown 5HT dysfunction to be associated with the symptoms of anxiety and depressive mood, and as some of our recent work has identified a strong linkage between suicidality, aggression, and anxiety, this may also suggest that the specificity of the biological variable (5HT disturbance) may be more closely related, on the functional or dimensional level, to psychopathological dysfunctions or symptoms such as suicidality, dysregulation of aggression, and anxiety, rather than to discrete nosological categories (i.e., depression).

Beyond Nosology in Biological Psychiatry. 5-HT Disturbances in Mood, Aggression and Anxiety Disorders

5-HT disorders have been reported in depression, anxiety states, schizophrenia and alcoholism. The increasing number of psychiatric states in which serotonin (5-hydrotryptamine; 5-HT) apparently can be disturbed seems bewildering. The situation has been called chaotic, the findings themselves non-specific. Van Kammen (1987) called 5-HT, ironically, a neurotransmitter of all seasons. We do not concur with either statement and in this chapter we explain why. First we discuss the available data; then we try to bring them into a conceptual framework.