Principles and Practice of Structural Equation Modeling (2nd ed.)

The discovery of neuroleptic drugs in 1952 provided a new strategy for seeking a biological basis of schizophrenia. This entailed a search for a primary site of neuroleptic action. The Parkinsonian effects caused by neuroleptics suggested that dopamine transmission may be disrupted by these drugs. In 1963 it was proposed that neuroleptics blocked "monoamine receptors" or impeded the release of monoamine metabolites. The neuroleptic concentration in plasma water or cerebrospinal fluid was of the order of 2 nM for haloperidol in clinical therapy. A systematic research was made between 1963 and 1974 for a primary site of neuroleptic action which would be sensitive to 2 nM haloperidol and stereoselective for (+)-butaclamol. Direct evidence that neuroleptics selectively blocked dopamine receptors occurred in 1974 with the finding that nanomolar concentrations of these drugs stereoselectively inhibited the binding of [3H]-dopamine or [3H]-haloperidol. These binding sites, now termed D2 dopamine receptors (which inhibit adenylate cyclase), are blocked by neuroleptics in direct relation to the antipsychotic potencies of the neuroleptics. No such correlation exists for D1 receptors (which stimulate adenylate cyclase). Based on the fact that dopamine-mimetic drugs elicited hallucinations, and that neuroleptics caused rigidity, Van Rossum in 1966 had suggested a hypothesis that dopamine pathways may be overactive in schizophrenia. The D2-selective blockade by all neuroleptics (except the monoamine-depleting reserpine) provided strong support for the dopamine hypothesis. Further support now comes from postmortem data and in vivo positron tomographic data, both of which indicate that the density of D2 receptors are elevated in the schizophrenic brain. The postmortem data indicate a bimodal pattern with half the schizophrenics having striatal D2 densities of 14 pmol/g (control is 13 pmol/g) and the other half having 26 pmol/g. Current positron tomographic data indicate D2 densities of 14 pmol/g in control subjects, but values of 34 pmol/g in drug-naive schizophrenics. Future tests of the dopamine hypothesis of schizophrenia may entail an examination of the amino acid composition and genes for D2 receptors in schizophrenic tissue, an examination of the ability of the D2 receptor to become phosphorylated and to desensitize into the low-affinity state, and an examination of the interaction of D2 receptors with D1 receptors or other neurotransmitters.

Dopamine receptors and the dopamine hypothesis of schizophrenia.

Context Psychopaths belong to a larger group of persons with antisocial personality disorder and are characterized by an inability to have emotional involvement and by the repeated violation of the rights of others. It was hypothesized that this behavior might be the consequence of deficient fear conditioning. Objective To study the cerebral, peripheral, and subjective correlates of fear conditioning in criminal psychopaths and healthy control subjects. Design An aversive differential pavlovian delay conditioning paradigm with slides of neutral faces serving as conditioned and painful pressure as unconditioned stimuli. Setting The Department of Medical Psychology at the University of Tubingen, Tubingen, Germany. Participants Ten male psychopaths as defined by the Hare Psychopathy Checklist–Revised and 10 age- and education-matched healthy male controls. The psychopaths were criminal offenders on bail and waiting for their trial or were on parole. The healthy controls were recruited from the community. Main Outcome Measures Brain activation based on functional magnetic resonance imaging, electrodermal responses, emotional valence, arousal, and contingency ratings. Results The healthy controls showed enhanced differential activation in the limbic-prefrontal circuit (amygdala, orbitofrontal cortex, insula, and anterior cingulate) during the acquisition of fear and successful verbal and autonomic conditioning. The psychopaths displayed no significant activity in this circuit and failed to show conditioned skin conductance and emotional valence ratings, although contingency and arousal ratings were normal. Conclusion This dissociation of emotional and cognitive processing may be the neural basis of the lack of anticipation of aversive events in criminal psychopaths.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/208744/yoa40213.pdf

Deficient Fear Conditioning in Psychopathy A Functional Magnetic Resonance Imaging Study

Violent offenders: Appraising and managing risk, 2nd ed.

Two hundred and eighty-three chronic pain patients, consecutive admissions to the Comprehensive Pain Center of the University of Miami School of Medicine, received an extensive psychiatric evaluation based upon the American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders (DSM-III) criteria and flowsheets. All patients received the following type of diagnoses: DSM-III axis I; DSM-III axis II, and personality type. The distribution of assigned diagnoses for the entire patient sample was reviewed and a statistical comparison between male and female patients was performed with regards to the prevalence of each diagnosis. Anxiety syndromes and depression of various diagnostic types were the most frequently assigned axis I diagnoses with over half the patient sample receiving each of these diagnoses. Males were significantly overrepresented in the axis I diagnoses of intermittent explosive disorders, adjustment disorders with work inhibitions, and alcohol abuse and other drug dependence, while females were significantly overrepresented in disorders of current depression of various diagnostic types and somatization disorders. 58.4% of the patients fulfilled criteria for axis II personality disorder diagnoses. The most frequently personality disorders found in the patient group were dependent (17.4%), passive aggressive (14.9%), and histrionic (11.7%). Males were significantly overrepresented in paranoid and narcissistic disorders while females were overrepresented in histrionic disorder. The most frequent personality types found in the patient group were compulsive (24.5%) and dependent (10.6%). All personality types were similarly distributed between the sexes. The results of the present study were compared to a previous study of DSM-III diagnoses in chronic pain patients and are discussed in terms of the prevalence of DSM-III diagnoses in the general population. Questions are raised as to the applicability of certain DSM-III diagnoses in the chronic pain population.

Male and female chronic pain patients categorized by DSM-III psychiatric diagnostic criteria

• A double-blind study of the behavioral effects of short-term naloxone hydrochloride administration was performed in 32 schizophrenic and 26 manic patients in a World Health Organization collaborative project. There was a significant naloxoneassociated reduction in overall physician-rated symptoms in schizophrenic patients concurrently treated with neuroleptic medication (N = 19) but not in medication-free schizophrenics (N = 13). Physician ratings of auditory hallucinations showed significant naloxone-associated improvement for the total schizophrenic population, while self-ratings of auditory hallucinations showed improvement only in neuroleptic-treated schizophrenics. While further studies are needed to delineate these effects as to clinical significance, they may bear etiological implications for the psychobiology of schizophrenia, including the possibility of synergistic effects of dopamine and endorphin blockade. Naloxone produced no significant behavioral effects in manic patients. These findings are discussed with relationship to the hypotheses of endorphin involvement in schizophrenia and mania.

Short-term Naloxone Administration in Schizophrenic and Manic Patients: A World Health Organization Collaborative Study

Mindestanforderungen für Schuldfähigkeitsgutachten

Assessing measurement invariance of PCL-R assessments from file reviews of North American and German offenders.

Introduction The VRAG is an actuarial risk assessment instrument, developed in Canada as an aid to estimating the probability of reoffending by mentally ill offenders.

Aim To test the predictive validity of the VRAG with a German sample.

Method The predictive validity of the VRAG was tested on a sample of 136 people charged with a criminal offence and under evaluation for criminal responsibility in the forensic psychiatry department at the University of Munich in 1994–95. The predicted outcome was tested by means of ROC analysis for correlation with the observed rate of recidivism between discharge after the 1994–95 assessment and the census date of 31 March 2003. Recidivism rate was calculated from the official records of the National Conviction Registry.

Results Just over 38% of the sample had reoffended by 2003. Their mean time-at-risk was 58 months (SD 3.391; range 0–115 months). The VRAG yielded a high predictive accuracy in the ROC analysis with an AUC of 0.703. For a constant time-at-risk < = 7 years, the predicted probability and observed rates of recidivism correlated significantly with Pearson's r = 0.941.

Conclusions The validity of the VRAG was replicated with a German sample. The VRAG yielded good predictive accuracy, despite differences in sample and outcome variables compared with its original sample. Copyright © 2007 John Wiley & Sons, Ltd.

The validity of the Violence Risk Appraisal Guide (VRAG) in predicting criminal recidivism.

A clear and structured approach to evidence-based and gender-specific risk assessment of violence in female offenders is high on political and mental health agendas. However, most data on the factors involved in risk-assessment instruments are based on data of male offenders. The aim of the present study was to validate the use of the Psychopathy Checklist Revised (PCL-R), the HCR-20 and the Violence Risk Appraisal Guide (VRAG) for the prediction of recidivism in German female offenders. This study is part of the Munich Prognosis Project (MPP). It focuses on a subsample of female delinquents (n?=?80) who had been referred for forensic-psychiatric evaluation prior to sentencing. The mean time at risk was 8 years (SD?=?5 years; range: 1–18 years). During this time, 31% (n?=?25) of the female offenders were reconvicted, 5% (n?=?4) for violent and 26% (n?=?21) for non-violent re-offenses. The predictive validity of the PCL-R for general recidivism was calculated. Analysis with receiver-operating characteristics revealed that the PCL-R total score, the PCL-R antisocial lifestyle factor, the PCL-R lifestyle factor and the PCL-R impulsive and irresponsible behavioral style factor had a moderate predictive validity for general recidivism (area under the curve, AUC?=?0.66, p?=?0.02). The VRAG has also demonstrated predictive validity (AUC?=?0.72, p?=?0.02), whereas the HCR-20 showed no predictive validity. These results appear to provide the first evidence that the PCL-R total score and the antisocial lifestyle factor are predictive for general female recidivism, as has been shown consistently for male recidivists. The implications of these findings for crime prevention, prognosis in women, and future research are discussed

Norbert Nedopil

Papers

Short-term Naloxone Administration in Schizophrenic and Manic Patients: A World Health Organization Collaborative Study

Mindestanforderungen für Schuldfähigkeitsgutachten

Assessing measurement invariance of PCL-R assessments from file reviews of North American and German offenders.

The validity of the Violence Risk Appraisal Guide (VRAG) in predicting criminal recidivism.

Recidivism in female offenders: PCL-R lifestyle factor and VRAG show predictive validity in a German sample.