Ejaculatory incompetence: a theoretical formulation and case illustration

Three theoretical formulations of ejaculatory incompetence have been proposed in the literature. They include: (1) aversive conditioned inhibition of the ejaculatory reflex, (2) an "autosexual" orientation associated with discrepant levels in the cognitive and physiological dimensions of sexual arousal, and (3) a discriminative learning model. These three models are discussed in relation to their theoretical and therapeutic implications. Clinical data supporting the discriminative view is presented.     

An immunohistochemical study of androgen, oestrogen and progesterone receptors in the vulva and vagina

Objective Tomap potential sites of sex steroid action in the human vulva.
Methods Monoclonal antibodies to androgen, oestrogen and progesterone receptors were used to stainfrozen sections of vulval skin, vagina and suprapubic skin. A scoring system was devised to comparereceptor distribution in the epidermis and dermis of skin with vaginal epithelium and stroma.
Results Androgen receptors were seen in epidermal keratinocytes, sebaceous glands, sweat glands, hairfollicles and dermal fibroblasts of skin, and epithelial cells and stromal fibroblasts of the vagina. Androgen receptor scores were significantly higher in the epidermis of labia majora and minora thanin vaginal epithelium. Oestrogen receptors were seen in basal and suprabasal cells of vaginalepithelium and epidermis of labia minora but were restricted to basal keratinocytes in true skin.They were seen in stromal fibroblasts and vaginal smooth muscle, and dermal fibroblasts of theskin. Oestrogen receptors were highest in vaginal epithelium and stroma, and lowest insuprapubic skin. Progesterone receptors were seen in vaginal epithelium, fibroblasts and smoothmuscle but not in the vulva. There was no evidence of significant differences in androgen oroestrogen receptor staining in the vulva of pre- or postmenopausal women.
Conclusion The transition from vagina to vulva is marked by an increase in androgen and a decrease inoestrogen and progesterone receptors. This distribution of receptors would indicate a limited role foroestrogen creams on the vulva.     

An unusual pattern of testosterone metabolism in tissue associated with a keratin-filled cutaneous cyst.

Testosterone metabolism was studied in tissues associated with a keratin-filled cutaneous cyst. Instead of the 5alpha-reduced metabolites usually associated with skin steroid metabolism, considerable amounts of 5beta-reduced steroids were found. These included 5beta-androstane-3,17-dione, 17beta-hydroxy-5beta-androstan-3-one, and 5beta-androstane-3beta,17beta-diol. This change in metabolic pattern is discussed.     

Androgen metabolism in skin and skeletal muscle of the rainbow trout (Salmo gairdnerii) and in accessory sexual organs of the spur dogfish (Squalus acanthias).

The in vitro metabolism of testosterone, 4-androstene-3,17-dione (androstenedione) and dehydroepiandrosterone by skin and muscle from the rainbow trout (Salmo gairdnerii), and by skin and accessory sexual tissues from the spur dogfish (Squalus acanthias) was studied. In trout skin, testosterone was transformed mainly into 5α-dihydrotestosterone together with smaller amounts of 5α-androstane-3α, 17β-diol, androstenedione, 5α-androstane-3,17-dione and androsterone. Androstenedione was transformed mainly into 5α-androstane-3,17-dione with smaller amounts of testosterone, 5α-dihydrotestosterone, androsterone and 5α-androstane-3α,17β-diol. Dehydroepiandrosterone was transformed to 5-androstene-3β,17β-diol with trace quantities of androstenedione and 5α-androstane-3,17-dione. Unidentified polar nonconjugated metabolites and traces of steroid glucuronides were formed from the three substrates. The patterns of steroid metabolism were similar in dorsal and ventral skin, and in dorsal skin from male and female, adult and immature fish. Most of the 5α-reductase activity in the skin was in the dermis, only a small fraction of the total activity being in the epidermis. The trout muscle converted testosterone into 5α-dihydrotestosterone but in much lower yields than did skin.The skin, clasper, sperm sac and vas deferens of an adult male spur dogfish converted testosterone to 5α-dihydrotestosterone and androstenedione, though in much lower yields than did trout skin. Androstenedione was converted into testosterone, 5α-androstane-3, 17-dione and androsterone, while dehydroepiandrosterone was converted into 5-androstene-3β,17β-diol. No metabolism of testosterone was detected in the skeletal muscle of the dogfish.     

Structural Brain Alterations Associated With Schizophrenia Preceded by Conduct Disorder: A Common and Distinct Subtype of Schizophrenia?

Conduct disorder (CD) prior to age 15 is a precursor of schizophrenia in a minority of cases and is associated with violent behavior through adulthood, after taking account of substance misuse. The present study used structural magnetic imaging to examine gray matter (GM) volumes among 27 men with schizophrenia preceded by CD (SZ+CD), 23 men with schizophrenia but without CD (SZ–CD), 27 men with CD only (CD), and 25 healthy (H) men. The groups with schizophrenia were similar in terms of age of onset and duration of illness, levels of psychotic symptoms, and medication. The 2 groups with CD were similar as to number of CD symptoms, lifelong aggressive behavior, and number of criminal convictions. Men with SZ+CD, relative to those with SZ–CD, displayed (1) increased GM volumes in the hypothalamus, the left putamen, the right cuneus/precuneus, and the right inferior parietal cortex after controlling for age, alcohol, and drug misuse and (2) decreased GM volumes in the inferior frontal region. Men with SZ+CD (relative to the SZ–CD group) and CD (relative to the H group) displayed increased GM volumes of the hypothalamus and the inferior and superior parietal lobes, which were not associated with substance misuse. Aggressive behavior, both prior to age 15 and lifetime tendency, was positively correlated with the GM volume of the hypothalamus. Thus, among males, SZ+CD represents a distinct subtype of schizophrenia. Although differences in behavior emerge in childhood and remain stable through adulthood, further research is needed to determine whether the differences in GM volumes result from abnormal neural development distinct from that of other males developing schizophrenia.Key words: conduct problems, antisocial behavior, violence, structural brain alterationsMany years ago, Lee Robins found that conduct disorder (CD) was a precursor of schizophrenia ¹ and later confirmed this finding. ^{2 , 3} Subsequent evidence concurs. For example, a prospective investigation that followed a birth cohort to age 26 determined that 40% of the cohort members who developed schizophreniform disorders had displayed CD prior to age 15. ⁴ The CD modules of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental (DSM) disorders (fourth edition, DSM-IV), SCID in short, were designed to diagnose CD prior to age 15 among adults. ⁵ Several studies have used this interview protocol, some supplementing self-reports with information from family members, school, social service, and justice files, to diagnose CD among adults with schizophrenia. Among men and women with schizophrenia in general psychiatric services, the prevalence of CD prior to age 15 ranged from 20% to 45%, ^{6 , 7} with higher rates in samples recruited from forensic hospitals and correctional facilities. ⁶ CD is a precursor of schizophrenia, and it is more common among people with schizophrenia than in the general population. ⁶ Among people with schizophrenia, CD prior to age 15 continues to be associated with antisocial and violent behavior through adult life after taking account of past and current substance misuse. ^6–12 Among people with schizophrenia, ^{10 , 13–17} as in the general population, ^18–20 those who present CD in childhood commit a disproportionate number of violent crimes. While some studies show that positive symptoms are associated with aggressive behavior even after taking account of CD, ²¹ those with CD are not distinguished from other patients with schizophrenia by profiles of positive and negative symptoms. ²² Prospective investigations show that adults with schizophrenia and prior CD (SZ+CD) displayed aggressive behavior, psychotic-like experiences as children, ²³ and poor academic achievement. ²⁴ Retrospective studies report that adults with SZ+CD, as compared to those with SZ–CD, obtained lower-than-average marks in elementary school, failed to graduate from secondary school, abused substances in adolescence, and experienced physical abuse. ^{6 , 24–27} Criminality and substance misuse are elevated among fathers and brothers of men with SZ+CD, whereas rates of mental illness are similar to that found among patients with SZ–CD. ^{6 , 27 , 28} Among the non–mentally ill men, a small group present CD from an early age, persistent antisocial and aggressive behavior through adulthood, and abnormalities in brain structure relative to healthy men. ^29–37 Results of structural magnetic resonance imaging studies (sMRI) measuring gray matter (GM) volumes are inconsistent regarding the type (larger or smaller) and regions of abnormality. ^{32 , 35–37} Among men with SZ+CD, however, there no studies. ^{38 , 39} A few studies of brain structure have been conducted among men with schizophrenia who display different ages of onset and patterns of aggressive behavior, including persistent aggressive behavior and poor response to antipsychotic medication, no previous aggressive behavior and 1 violent offence, no aggressive behavior prior to onset followed by persistent aggression, and finally the largest group comprising those who show conduct problems from childhood that persist across their life span. The extant literature is limited and difficult to aggregate, but it does suggest differences specific to each pattern of violent behavior. ^38–43 Two studies examined male offenders with schizophrenia: one compared those with and without comorbid antisocial personality disorder (ASPD), which requires, by definition, CD prior to age 15; ⁴⁴ and another compared those with and without high psychopathy scores. ⁴⁵ Both included small samples and reported fewer neuropsychological deficits among the antisocial participants in tests tapping the dorsolateral prefrontal and the orbital frontal cortex (OFC) functions. ³⁸ A recent meta-analysis reported that among persons with schizophrenia, those defined very broadly as antisocial, as compared to the nonantisocial, were characterized by lower intelligence quotients (IQs) and memory dysfunction, whereas compared to non–mentally ill antisocial participants, they exhibited deficits in IQ, attention, executive function, and memory. ⁴⁶ Among patients with schizophrenia, scores on the Life History of Aggression (LHA) measure were associated with increased diffusivity in the inferior frontal white matter and lower functional connectivity between the amygdala and the ventral prefrontal cortex. ³⁹ Diffusivity has been associated with increased cerebrospinal fluid (CSF). ⁴⁷ Functional MRI (fMRI) studies of violent offenders with schizophrenia observed decreased frontal basal activation during a Go/NoGo task, increased activity in the motor, premotor, and anterior cingulate regions among those with ASPD, ⁴⁸ and attenuated amygdala activation to fearful faces among those with high psychopathy scores. ⁴⁹ Thus, among men with schizophrenia, at least one in five people presents CD prior to age 15 and persistent antisocial and aggressive behavior. Identifying distinctive subtypes of schizophrenia may facilitate etiological research ⁵⁰ and inform the development of effective treatments for both the illness and the antisocial and aggressive behavior. ⁵¹ Both schizophrenia ⁵² and CD ^{53 , 54} are neurodevelopmental disorders. In both disorders, from conception onwards, combinations of genes, in addition and in interaction with environmental events, are thought to modify brain structure and function. Thus, we reasoned that when schizophrenia develops in parallel with CD, neurodevelopment would be distinct from both that associated with schizophrenia and that associated with CD. We hypothesized that in adulthood, men with SZ+CD would show cognitive and structural brain abnormalities relative to healthy men, and both similarities and differences relative to men with SZ–CD and those with CD and no mental illness.Almost all persons with childhood onset of CD and persistence of antisocial and aggressive behavior in adulthood also display childhood onset and persistent pattern of substance misuse. ^55–57 This is true among those with and without schizophrenia. ^{22 , 26–28} Although substance misuse is an integral part of a heritable pattern of lifelong antisocial behavior, ⁵⁸ disentangling the cognitive and structural abnormalities consequent to substance use from those associated with persistent antisocial and aggressive behavior is necessary to understand the mechanisms underlying these behaviors. However, neither statistical controls nor studying groups of antisocial persons without substance misuse provide an ideal solution to this problem. ⁵⁹ Further, prospective studies indicate that heavy cannabis use in adolescence may play a causal role in schizophrenia ^{60 , 61} by altering brain development, ^{62 , 63} and 1 study has shown that among persons experiencing a first episode of psychosis, CD increased the likelihood of cannabis use before age 14. ⁶⁴ In addition, histories of substance misuse that can be obtained from middle-aged adults are imprecise measures of different phenomena—past and current use by type, combinations, and doses of substances. This led us to obtain careful histories of use of substances and to statistically control for group differences in use.Four groups of men, with SZ+CD, SZ–CD, CD, and no schizophrenia or history of CD (H), were compared on sociodemographic, clinical, and forensic characteristics, and their GM brain volumes were assessed using sMRI.