CSF studies in violent offenders. I. 5-HIAA as a negative and HVA as a positive predictor of psychopathy.

Low serotonin activity in man has been related to impulsive, self-destructive violence but not to instrumental aggression aimed at dominance. A relationship has also been suggested between aggression and high catecholaminergic activity. Several studies have reported signs of aberrant dopaminergic function in attention deficit hyperactivity disorder, autism, and schizophrenia. In 22 violent offenders undergoing pretrial forensic psychiatric investigation, interpersonal and behavioral features of psychopathy, measured by the Psychopathy Checklist Revised (PCL-R), were significantly predicted by low cerebrospinal fluid (CSF) concentrations of 5-HIAA and high CSF concentrations of HVA in multivariate regression models. CSF concentrations of MHPG did not contribute to the model. This seems to link the outward-directed aggression of psychopathy to serotonergic hypofunctioning and high dopamine turnover, which might account for disinhibition of destructive impulses.

CSF studies in violent offenders. II. Blood-brain barrier dysfunction without concurrent inflammation or structure degeneration.

Cerebral dysfunction without corresponding structural pathology has been reported in brain imaging studies of violent offenders. Biochemical markers in the CSF reflect various types of CNS pathology, such as blood-brain barrier dysfunction (CSF/S albumin ratio), infectious or inflammatory processes (IgG and IgM indices), neuronal or axonal degeneration (CSF-tau protein) and synaptic de- or regeneration (CSF-growth associated protein-43 (GAP-43)). We compared these CSF markers in 19 non-psychotic perpetrators of severe violent crimes undergoing pretrial forensic psychiatric investigation and 19 age- and sex-matched controls. Index subjects had significantly higher albumin ratios (p = 0.002), indicating abnormal vascular permeability as part of the complex CNS dysfunction previously reported in violent offenders. Axis I disorders, including substance abuse or current medication, did not explain this finding. Since Ig-indices, CSF-tau protein or CSF-GAP-43 were not increased, there was no support for inflammation or neuronal/synaptic degeneration as etiological factors to CNS dysfunction in this category of subjects.