Serena-Lynn Brown

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.

Therapeutic indications for serotonin-potentiating compounds: A hypothesis

The original antidepressants, tricyclics and MAO inhibitors, increase the availability in the brain of both 5-HT and NA. Prompted by clinical findings suggestive of 5-HT disturbances in depression, drugs were developed that increase 5-HT selectively. Data are presented that suggest that broad-spectrum compounds may provide better conditions for antidepressant effects than the 5-HT-selective ones. The hypothesis is proposed that 5-HT potentiators are partial antidepressants, in that they predominantly reduce the anxiety/aggressive component of the depressive syndrome, and deserve to be tested in conditions with heightened anxiety and/or aggression irrespective of the nosological diagnosis. Tentative evidence relates diminished 5-HT metabolism to disordered impulse control. Based on these data, trials of 5-HT potentiators in impulse control disorders unrelated to aggressive drives seem warranted.

Correlates of suicide and violence risk in an inpatient population: Coping styles and social support

Forty-six suicidal psychiatric inpatients were compared with 44 nonsuicidal psychiatric inpatients on measures of suicide risk, violence risk, impulsivity, feelings of anger, social support, and eight coping styles. The two groups were similar on demographic variables, but the suicidal patients were higher on the suicide risk scale, the violence risk scale, the impulsivity scale, and feelings of anger. Suicidal patients were significantly less likely to use the coping style of minimization to deal with life problems. A negative correlation was found between the social support measure and both suicide risk and violence risk. Three coping styles were found to correlate negatively with violence risk, but none with suicide risk. Coping styles were found to be a better predictor of violence risk than of suicide risk. It was also found that the more variables included in the predictor equation, the higher the correlation with the risk measures.

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 neuroendocrine challenge paradigm in headache research

The neuroendocrine challenge paradigm provides a “window” on central neurotransmitter function in vivo. This strategy is based on the premise that the sensitivity of certain central receptors can be inferred from the magnitude of the hormonal response to specific pharmacologic probes. For example, the serotonin (5HT) receptor agonist m-chlorophenylpiperazine (m-CPP) stimulates the release of cortisol and prolactin and induces migraine-like headaches. We have previously reported that the headache and cortisol responses to m-CPP are highly correlated, which may implicate a disturbance in central serotonergic neurotransmission in the pathogenesis of migraine. As pharmacologic probes with greater specificity for 5HT receptor subtypes become available, we may be able to elucidate these mechanisms with greater precision. The neuroendocrine challenge methodology is also applicable to the study of other neurotransmitter systems and other headache disorders.

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.

Suicide: CSF and neuroendocrine challenge studies

This paper summarizes current cerebrospinal fluid and neuroendocrine challenge research on the role of serotonin, norepinephrine, dopamine, and the hypothalamic-pituitary-adrenal axis in relation to suicidality. At present, the only compelling evidence for neurotransmitter or hormonal dysregulation in suicide comes from the data on serotonin. While early research implicated serotonergic dysfunction in depressive disorder, subsequent data have suggested more strongly that serotonergic dysfunction might be more directly related to suicidality in depression, than to suicidality in general, and now, more recently, to dysregulation of aggression, both inwardly-and outwardly-directed. Implications for such findings are discussed.