Wernicke-Kleist-Leonhard phenotypes of endogenous psychoses: a review of their validity
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While the ICD-DSM paradigm has been a major advance in clinical psychiatry, its usefulness for biological psychiatry is debated. By defining consensus-based disorders rather than empirically driven phenotypes, consensus classifications were not an implementation of the biomedical paradigm. In the field of endogenous psychoses, the Wernicke-Kleist-Leonhard (WKL) pathway has optimized the descriptions of 35 major phenotypes using common medical heuristics on lifelong diachronic observations. Regarding their construct validity, WKL phenotypes have good reliability and predictive and face validity. WKL phenotypes come with remarkable evidence for differential validity on age of onset, familiality, pregnancy complications, precipitating factors, and treatment response. Most impressive is the replicated separation of high- and low-familiality phenotypes. Created in the purest tradition of the biomedical paradigm, the WKL phenotypes deserve to be contrasted as credible alternatives with other approaches currently under discussion.
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Cocaine craving is associated with electrophysiological brain responses to cocaine-related stimuli.

Several studies show that substance dependence disorders are characterized by an enhanced processing of substance-related stimuli. The present study was designed to examine the association between craving levels and selective processing of drug cues in cocaine-dependent patients using event-related brain potentials (ERPs). In abstinent cocaine-dependent patients and a healthy control group, we studied the late positive potential (LPP) amplitudes elicited by neutral and cocaine-related stimuli. The results show that cocaine-dependent patients have an enhanced electrophysiological response in the late LPP time window to cocaine-related stimuli as compared to controls, suggesting an enhanced processing of these stimuli. Most importantly, a robust association was observed between cocaine craving and LPP amplitude. High craving levels were associated with larger LPP amplitudes at central electrode sites in the right hemisphere. These findings are in line with theories linking motivational aspects and appetitive stimulus processing. Furthermore, it is demonstrated that ERPs are a useful index to assess motivational properties of stimuli in cocaine-dependent patients. These findings suggest that electrophysiological measures may have clinical relevance in substance use disorders.

Prenatal exposure to the 1944-45 Dutch 'hunger winter' and addiction later in life.

AIMS: Prenatal exposure to severe famine has been associated with an increased risk of schizophrenia and affective disorders. We studied the relationship between prenatal exposure to famine during the Dutch hunger winter of 1944-45 and addiction later in life. DESIGN: A case-control study. SETTING: The Rotterdam city area during the Dutch hunger winter lasting from mid-October 1944 to mid-May 1945. From February 1945 to mid-May 1945 the hunger winter was characterized by a famine peak. PARTICIPANTS: Patients are native Dutch addicted patients from the Rotterdam Addiction Treatment Program and controls are native Dutch inhabitants of Rotterdam, born between 1944 and 1947. MEASUREMENT: Exposure to the whole hunger winter (< 1400 kcal/day) and the peak of the hunger winter (< 1000 kcal/day) was determined for each trimester of gestation. For each trimester the exposed/unexposed ratios were compared between patients and controls and quantified as odds ratios (OR). FINDINGS: The odds of first-trimester gestational exposure to famine during the total hunger winter was significantly higher among patients receiving treatment for an addictive disorder [OR = 1.34, 95% confidence interval (CI) 1.10-1.64]. Stratification by sex shows that the odds of exposure during the first trimester was significantly higher only among men (OR = 1.34, 95% CI 1.05-1.72), but not among women (OR = 1.26, 95% CI 0.88-1.81). The odds of exposure to the peak of the hunger winter during the first trimester of gestation were also significantly higher among addiction treatment patients (OR = 1.61, 95% CI 1.22-2.12). We did not find any significant differences for the second and third trimesters of gestation. CONCLUSION: First-trimester prenatal exposure to famine appears to be associated with addiction later in life. The study confirms the adverse influence of severe malnutrition on brain development and maturation, confirms the influence of perinatal insults on mental health in later life and gives rise to great concern about the possible future consequences for the hunger regions in our world.

Error-processing deficits in patients with cocaine dependence.

Cocaine abuse and addiction can be characterized by a persisting use of cocaine in the face of adverse consequences. In the present study we focus on one specific element of adverse consequences: the making of errors. The aim of this study was to determine whether cocaine-dependent persons have error-processing deficits as measured using error-related negativity (ERN) and error positivity (Pe). Event-related potentials (ERPs) during an Eriksen flanker task were recorded from cocaine-dependent patients and a control group. Cocaine-addicted patients showed reduced ERN and Pe components as compared to a control group. On the behavioral level, patients showed reduced post-error accuracy improvement. The present findings reveal that cocaine addiction is associated with reduced error processing and impaired behavioral correction of errors after an error is made. These deficits may be associated with a compromised dopamine system. It is argued that these cognitive deficits may contribute to the maintenance of the cocaine addiction.