[Sexual disorders in the DSM-5]. / Seksuele stoornissen in de DSM-5.

BACKGROUND: In DSM-IV-TR, the subject of 'sexual and gender identity disorders' was dealt with in one chapter; in DSM-5, however, the subject is divided into three chapters, namely sexual dysfunctions , gender dysphoria, and paraphilic disorders. AIM: To discuss the above-mentioned changes. METHOD: The one-chapter version in DSM-IV is compared with the three-chapter contribution in DSM-5 and the differing criteria are tested for their clinical utility. RESULTS: There are minor changes in the chapter 'sexual dysfunctions'. The content of the chapters on 'gender dysphoria' and 'paraphilic disorders' differs substantially from the content of the sections on these subjects in DSM-IV. In the section on gender dysphoria the term 'sex' has been replaced by 'gender' and the term 'identity disorder' has been dropped. With regard to paraphilias, a distinction is now made between a paraphilia and a paraphilic disorder. The DSM-5 makes a new distinction between pathology (paraphilic disorder) on the one hand and other unusual or unconventional non-pathological sexual behavior on the other hand. In the DSM-5 the highly relevant clinical concept 'hypersexuality' has still not been incorporated as a separate category. CONCLUSION: In the DSM-5 many parts of the chapters on sexual disorders have been substantially revised.

Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience.

Psychiatric neurosurgery teams in the United States and Europe have studied deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule and adjacent ventral striatum (VC/VS) for severe and highly treatment-resistant obsessive-compulsive disorder. Four groups have collaborated most closely, in small-scale studies, over the past 8 years. First to begin was Leuven/Antwerp, followed by Butler Hospital/Brown Medical School, the Cleveland Clinic and most recently the University of Florida. These centers used comparable patient selection criteria and surgical targeting. Targeting, but not selection, evolved during this period. Here, we present combined long-term results of those studies, which reveal clinically significant symptom reductions and functional improvement in about two-thirds of patients. DBS was well tolerated overall and adverse effects were overwhelmingly transient. Results generally improved for patients implanted more recently, suggesting a 'learning curve' both within and across centers. This is well known from the development of DBS for movement disorders. The main factor accounting for these gains appears to be the refinement of the implantation site. Initially, an anterior-posterior location based on anterior capsulotomy lesions was used. In an attempt to improve results, more posterior sites were investigated resulting in the current target, at the junction of the anterior capsule, anterior commissure and posterior ventral striatum. Clinical results suggest that neural networks relevant to therapeutic improvement might be modulated more effectively at a more posterior target. Taken together, these data show that the procedure can be successfully implemented by dedicated interdisciplinary teams, and support its therapeutic promise.

[Fitting proof]. / Passend bewijs.

Randomised controled trials (RCT's) and meta analyses of RCT's are known as the best research designs to evaluate if interventions are doing more good than bad. Some interventions can not be evaluated by RCT's because of the heterogeneity of the problems, the cost of the evaluation study or ethical arguments against the study. This is often the case with population based interventions. A typical example is suicide prevention. The shortcomings of the "classic" research designs for the evaluation of suicide prevention are discussed and feasible solutions are suggested for future research.

Applicants for stereotactic neurosurgery for psychiatric disorders: role of the Flemish advisory board.

OBJECTIVE: Research on stereotactic neurosurgery for psychiatric disorders (SNPD) is rapidly evolving. Knowledge on patients undergoing SNPD is of crucial importance. We describe applicants for SNPD and examine the necessity for a multidisciplinary advisory board. METHOD: Summary of the current practice of the Flemish advisory board (SNPD committee) and analysis of a questionnaire investigating the attitude of clinicians on SNPD. RESULTS: In 7 years, 91 applications were submitted, nine patients did not fulfill diagnostic criteria for OCD, 65 patients received a positive recommendation, 50 SNPD procedures were performed. The prevalence of SNPD in the current year in Belgium is 0.6/million inhabitants. Ninety-seven per cent of clinicians consider the expertise and advice of the SNPD committee essential for indication setting. Forty-four percent of clinicians consider referral of a patient for capsulotomy, 82% for electrical brain stimulation. CONCLUSION: Neurosurgery is exclusively considered for severe, treatment-refractory psychiatric disorders. Clinicians consider the SNPD committee essential in the decision-making process prior to intervention.

[Mentally disturbed offenders in Flanders]. / De justitiabele met een psychische stoornis in Vlaanderen.

In the course of the past 25 years in Flanders there has been a real breakthrough as far as forensic psychiatry is concerned. New types of treatment have become available for mentally disturbed offenders, whether they are in prison or in the community. A new Belgian law on mentally disturbed offenders with diminished responsibility confirms that 'internment' is still regarded as a protective measure and an alternative to punishment. The current university course in psychiatry should now be widened to include the subject of forensic mental health.

Behavioural and physiological effects of electrical stimulation in the nucleus accumbens: a review.

Electrical stimulation (ES) in the brain is becoming a new treatment option in patients with treatment-resistant obsessive-compulsive disorder (OCD). A possible brain target might be the nucleus accumbens (NACC). This review aims to summarise the behavioural and physiological effects of ES in the NACC in humans and in animals and to discuss these findings with regard to neuroanatomical, electrophysiological and behavioural insights. The results clearly demonstrate that ES in the NACC has an effect on reward, activity, fight-or-flight, exploratory behaviour and food intake, with evidence for only moderate physiological effects. Seizures were rarely observed. Finally, the results of ES studies in patients with treatment-resistant OCD and in animal models for OCD are promising.

Seasonal variation in plasma L-tryptophan availability in healthy volunteers. Relationships to violent suicide occurrence.

OBJECTIVE: To investigate the seasonal variation in levels of plasma L-tryptophan and competing amino acids (CAAs) in healthy humans in relation to climatic variables, total serum protein levels, and violent suicide occurrence. METHODS: Twenty-six healthy volunteers (13 men and 13 women; mean [+/- SD] age, 38.7 +/- 13.4 years) had monthly blood samplings for assays of L-tryptophan, valine, leucine, isoleucine, tyrosine, and phenylalanine during 1 calendar year. RESULTS: Significant annual rhythms were detected in L-tryptophan, the L-tryptophan/CAA ratio, phenylalanine, valine, and leucine, and semiannual rhythms in L-tryptophan values and in L-tryptophan/CAA ratios. Plasma L-tryptophan and the L-tryptophan/CAA ratio were significantly lower in the spring than in the other seasons. The peak-trough differences in the yearly variation expressed as a percentage of the mean were 17.1% and 16.1% for L-tryptophan values and L-tryptophan/CAA ratios, respectively. The amplitude of the yearly variation in all CAAs was low, ie, less than 7%. An important part of the variance in L-tryptophan availability (ie, 12% to 14%) could be explained by the composite effects of present and past climatic factors; higher ambient temperature and relative humidity in the face of lower air pressure are the most important predictors of low L-tryptophan availability. Important and positive time relationships were noted between total serum protein level and all amino acid concentrations, and a significant time relationship was also noted between the seasonal variation in L-tryptophan availability and the occurrence of violent suicide in Belgium. CONCLUSION: Our results show a bimodal seasonal pattern in the availability of plasma L-tryptophan that matches seasonal patterns in the prevalence of violent suicide in the local population and depression in other studies.

Relationships between increased haptoglobin plasma levels and activation of cell-mediated immunity in depression.

Recently, it was found that major depression is accompanied by an acute phase (AP) response with increased haptoglobin (Hp) plasma levels and various indices of systemic immune stimulation. The present study has been carried out in order to determine the relationships between hyperhaptoglobinemia and indices of systemic immune activation in severe depression. Toward this end, the authors investigated the relationships between Hp levels and number of leukocytes, monocytes, neutrophils, lymphocytes, and activated T lymphocytes (CD25+, HLA-DR+), in depression. Hp plasma levels were significantly higher in major depressed subjects as compared to healthy controls and minor depressives. There was a significant positive correlation between Hp levels and severity of illness. Hp plasma levels showed significant and positive relationships with the absolute number of leukocytes, neutrophils, monocytes, CD25+ and HLA-DR+ T cells. Up to 35% of the variance in Hp levels could be explained by the regression on the number of neutrophils and HLA-DR+ T cells. The results show that hyperhaptoglobinemia in major depression is significantly related to activation of cell-mediated immunity.

Lower serum prolyl endopeptidase enzyme activity in major depression: further evidence that peptidases play a role in the pathophysiology of depression.

Prolyl endopeptidase (PEP) is a serine proteinase, which may cleave peptides that are involved in the pathophysiology of major depression, such as arginine vasopressin, beta-endorphin, luteinizing hormone-releasing hormone, thyrotropin-releasing hormone, and maybe corticotropin-releasing hormone. PEP may be involved in activation of cell-mediated immunity, autoimmune and inflammatory responses, which repeatedly occur in severe depression. The present study investigates serum PEP activity in 33 normal controls, 16 minor, 14 simple major, and 18 melancholic depressed subjects. Pre-dexamethasone and post-dexamethasone (DST) intact adrenocorticotropic hormone (ACTH) and cortisol values were determined in 33 depressed subjects. Serum PEP activity was significantly lower in depressed subjects compared to normal controls and in melancholic depressed subjects compared to minor and simple major depressed subjects. Up to 61.1% of the melancholic patients had serum PEP activities below the mean PEP values of normal controls minus two SDs. In the depressed study group, significant negative correlations between serum PEP activity and severity of illness, post-DST cortisol, and ACTH values were observed. There was a trend toward higher serum PEP activity with increasing age. It is hypothesized that lower serum PEP activity, and lower serum activity of other peptidases, may play a role in the neuroendocrine and immune pathophysiology of major depression.

Pituitary and adrenal hormone responsiveness to Synacthen in melancholic subjects versus subjects with minor depression.

Increased adrenal cortex responsiveness to adrenocorticotropic hormone (ACTH) has been suggested to contribute to increased cortisol secretion in dexamethasone nonsuppression and melancholia. To further examine this hypothesis, the following variables were examined in 68 patients with unipolar depression (minor, n = 24; simple major, n = 25; melancholic, n = 19): basal or post-Synacthen [ACTH(1-24), 250 micrograms IV] intact ACTH(1-39), beta-endorphin/beta-lipotropin, cortisol, and androstenedione concentrations, as well as the postdexamethasone (DST) plasma ACTH(1-39) and cortisol values. Melancholic subjects showed significantly higher baseline ACTH(1-39), beta-endorphin/beta-lipotropin, and androstenedione values compared with subjects with minor depression. No significant differences in post-Synacthen cortisol or androstenedione secretion between any of the groups or between [ACTH(1-39) or cortisol] DST nonsuppressors and suppressors were found. No significant relationships between DST and ACTH test results were observed. Abnormally increased post-DST cortisol values in melancholic subjects were highly predicted (> 68% of the variance) by post-DST intact ACTH levels. ACTH(1-39) values were significantly lower after Synacthen administration in melancholic subjects than in subjects with minor depression. These results are not consistent with the hypothesis that melancholia is characterized by an increased adrenocortical responsivity to exogenous ACTH compared with minor depression or that DST nonsuppression is due to adrenal hyperresponsiveness.

Neutrophil chemotaxis, phagocytosis, and superoxide release in depressive illness.

Recently, some authors have reported defective neutrophil phagocytosis during depression. The present study investigated neutrophil function in 19 healthy controls and in 41 depressed inpatients categorized according to DSM-III into minor, simple major, and melancholic depression. We determined neutrophil function by means of phagocytosis, chemotaxis, and superoxide release. The results show no significant differences in neutrophil function among any of the subtypes of depression and normal volunteers. This suggests that overall neutrophil function is normal during depression. Thus, neutrophils are unlikely to be involved in the increased susceptibility to physical illness of patients with depression.

Seasonality in violent suicide but not in nonviolent suicide or homicide.

OBJECTIVE: Previous studies have reported seasonal or monthly variation in suicide. The present study was conducted in order to determine seasonality and other significant rhythms in violent and nonviolent suicide, alone and together, and homicide. METHOD: Data on suicide, violent suicide, nonviolent suicide, and homicide (categorized according to ICD-9) for all of Belgium for the period 1979-1987 were analyzed by means of spectral analyses. RESULTS: There was a significant seasonality for suicide but not homicide. Seasonality was present in violent but not in nonviolent suicide. The number of violent suicides increased with age and was more prominent in men. The violent suicide chronograms of younger and elderly persons were quite distinct in the occurrence of peaks in March-April and August, respectively, and lows in December-January. There was no significant relationship between violent suicide and homicide. CONCLUSIONS: Seasonality in suicide is determined by significant circannual rhythms in violent suicides, which differ between younger and elderly persons.

Haptoglobin phenotypes and gene frequencies in unipolar major depression.

OBJECTIVE: Studies from the authors' laboratory have shown that major depression is accompanied by significantly increased plasma concentrations of positive acute-phase proteins such as haptoglobin. Haptoglobin is characterized by a molecular variation with three known phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2). This study investigated haptoglobin plasma levels and phenotype and gene frequencies in unipolar major depression. METHOD: Haptoglobin plasma levels of 22 healthy volunteers, 32 patients with minor depression, and 72 patients with major depression were determined by means of a laser nephelometric method. Haptoglobin phenotyping of these 126 subjects and 200 healthy blood donors was also carried out. RESULTS: The patients with major depression exhibited significantly higher haptoglobin plasma levels than the healthy comparison subjects and the patients with minor depression. Subjects with the haptoglobin phenotype Hp 2-2 had significantly lower haptoglobin levels than the phenotype Hp 1-1 and Hp 2-1 carriers. The frequencies of haptoglobin phenotypes Hp 2-1 (61.1%) and Hp 2-2 (20.8%) in the patients with major depression were significantly higher and lower, respectively, than the frequencies in the normal population (i.e., the blood donors: 48.0% and 37.0%, respectively). The frequency of the Hp-1 gene was significantly greater in the patients with major depression (48.6%) than in the normal population (39.0%). CONCLUSIONS: Major depression is characterized by a hyperhaptoglobinemia that is largely independent of haptoglobin phenotypes. This altered distribution of haptoglobin phenotypes and genes suggests that genetic variation on chromosome 16 may be associated with that illness.

Stimulatory effects of L-5-hydroxytryptophan on postdexamethasone beta-endorphin levels in major depression.

Recently it has been shown that acute administration of 200 mg L-5-hydroxytryptophan (L-5-HTP) PO may increase post-dexamethasone (DST) adrenocorticotropic hormone (ACTH) and cortisol levels in major, but not minor, depressed subjects. This study aimed to examine the effects of 200 mg L-5-HTP PO on post-DST beta-endorphin levels in the same depressed subjects. It was found that in major, but not minor, depressed subjects, L-5-HTP significantly increased post-DST beta-endorphin concentrations as compared to placebo. The L-5-HTP-induced post-DST beta-endorphin responses were significantly higher in major than in minor depressed subjects. There was a significant and positive relationship between L-5-HTP-induced post-DST beta-endorphin and ACTH or cortisol responses. There was a significant and positive relationship between L-5-HTP-induced post-DST beta-endorphin values and the Hamilton Depression Rating Scale (HDRS) score. The results show that the acute administration of L-5-HTP may increase the escape of beta-endorphin secretion from suppression by dexamethasone in major, but not minor, depression.

Lower baseline plasma cortisol and prolactin together with increased body temperature and higher mCPP-induced cortisol responses in men with pedophilia.

There is some evidence that hormonal and serotonergic alterations may play a role in the pathophysiology of paraphilias. The aims of the present study were to examine: 1) baseline plasma cortisol, plasma prolactin, and body temperature; and 2) cortisol, prolactin, body temperature, as well as behavioral responses to meta-chlorophenylpiperazine (mCPP) and placebo in pedophiles and normal men. Pedophiles showed significantly lower baseline plasma cortisol and prolactin concentrations and a higher body temperature than normal volunteers. The mCPP-induced cortisol responses were significantly greater in pedophiles than in normal volunteers. In normal volunteers, mCPP-induced a hyperthermic response, whereas in pedophiles no such response was observed. mCPP induced different behavioral responses in pedophiles than in normal men. In pedophiles, but not in normal men, mCPP increased the sensations "feeling dizzy, " "restless," and "strange" and decreased the sensation "feeling hungry". The results suggest that there are several serotonergic disturbances in pedophiles. It is hypothesized that the results are compatible with a decreased activity of the serotonergic presynaptic neuron and a 5-HT2 postsynaptic receptor hyperresponsivity.

Lower serum L-tryptophan availability in depression as a marker of a more generalized disorder in protein metabolism.

Recently, it has been reported that major and melancholic depression are accompanied by a lower availability of total L-tryptophan (L-TRP) to the brain and by significant changes in electrophoretically separated protein fractions, such as albumin and alpha 2-globulin. The aim of this study was to examine the relationships between serum L-TRP availability and total serum protein, albumin, and alpha 2-globulin in 42 depressed and 24 normal subjects. In depressed and normal subjects, alone and together, there were significant and positive correlations between serum L-TRP and total serum protein or albumin concentrations. In the depressed subjects, but not in normal controls, there were significant inverse relationships between the L-TRP/competing amino acid ratio and the alpha 2-globulin fraction. Serum L-TRP and albumin were significantly lower in melancholic subjects than in normal and minor depressed subjects. Depressed subjects had a significantly lower L-TRP/competing amino acid ratio and significantly higher serum alpha 2-globulin than normal controls. Total serum protein was significantly lower in major depressed subjects than in normal controls. The results suggest that lower L-TRP availability to the brain in depression is related to lower serum albumin and to increased alpha 2-globulin fraction, which are both hallmarks of the acute phase response in depression. the results further corroborate the hypothesis that lowered L-TRP availability in depression is related to the acute phase response in that illness.

An evaluation of basal hypothalamic-pituitary-thyroid axis function in depression: results of a large-scaled and controlled study.

In order to evaluate the function of the hypothalamic-pituitary-thyroid (HPT)-axis in unipolar depression, the authors measured basal 0800h plasma levels of free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) by means of the new, ultrasensitive assays (TSH-IRMA) in 69 healthy controls, 62 minor, 101 simple major, and 57 melancholic depressed subjects. Basal HPT-axis hormone levels of almost all (96.8%) unipolar depressed patients fell within the normal, euthyroid range. None of the major depressed subjects showed subclinical hypothyroidism. It was found that 8.8% of the melancholic subjects exhibited some degree of subclinical hyperthyroidism. Basal TSH-IRMA values were significantly lower in melancholic patients than in healthy controls, minor and simple major depressed patients, and in major vs. minor depressed subjects. FT4 circulating levels were significantly higher in melancholic patients than in all other subjects. Basal TSH-IRMA and FT4 levels were significantly correlated with severity of illness. In depression, there was a significant and negative correlation between basal TSH-IRMA values and FT4 concentrations. No significant gender- or age-related differences in TSH-IRMA or thyroid hormones were detected in depression. It is argued that--in depression research--the assays of basal TSH-IRMA should replace thyrotropin releasing hormone tests.

Effects of serotonin precursors on the negative feedback effects of glucocorticoids on hypothalamic-pituitary-adrenal axis function in depression.

In order to investigate the relationships between brain serotonergic turnover and hypothalamic-pituitary-adrenal (HPA) axis function in unipolar depression, the authors measured intact adrenocorticotropic hormone (ACTH) and cortisol levels in baseline conditions and after combined dexamethasone (1 mg PO) and L-5-hydroxytryptophan (L-5-HTP, 200 mg PO) administration in 13 minor, 17 simple major, and 17 melancholic subjects. L-5-HTP significantly enhanced post-DST ACTH and cortisol secretion in major--but not in minor--depressed subjects. Major depressed subjects with or without melancholia exhibited significantly higher post-DST ACTH and cortisol responses to L-5-HTP than minor depressed subjects. L-5-HTP administration converted some major depressed ACTH or cortisol suppressors into nonsuppressors. L-5-HTP stimulated ACTH or cortisol secretion to the same extent in major depressed HPA-axis suppressors and nonsuppressors. It is concluded that L-5-HTP loading may augment ACTH and, consequently, cortisol escape from suppression by dexamethasone in major but not in minor depressed subjects. The findings show that serotonergic mechanisms modulate the negative feedback of glucocorticoids on central HPA-axis regulation. It is hypothesized that the higher L-5-HTP-induced post-DST HPA-axis hormone responses in major depression reflect upregulated 5-HT2 receptor-driven breakthrough secretion of pituitary ACTH from suppression by dexamethasone.

Acute administration of buspirone increases the escape of hypothalamic-pituitary-adrenal-axis hormones from suppression by dexamethasone in depression.

Recently, our laboratory found a significant enhancing effect of L-5-hydroxy-tryptophan (L-5-HTP) on post-dexamethasone (DST) plasma adrenocorticotropic hormone (ACTH) and cortisol levels in major-but not in minor-depression. To further elucidate the effects of central serotonin (5-HT) activity on the negative feedback of glucocorticoids on hypothalamic-pituitary-adrenal (HPA)-axis function in depression, this study investigates the effects of buspirone, a 5-HT1A receptor agonist, on post-DST ACTH and cortisol levels in 75 depressed subjects. Plasma post-DST ACTH and cortisol concentrations were significantly increased by the acute administration of buspirone (30 mg PO) compared to placebo. There were no differences in buspirone-induced post-DST ACTH or cortisol responses between minor and major depression. There were significant correlations between post-DST ACTH and cortisol, and between post-DST-buspirone ACTH and cortisol. The buspirone-induced post-DST cortisol responses were significantly higher in depressed women than men. It is concluded that buspirone may augment ACTH and, consequently, cortisol escape from suppression by dexamethasone in major as well as in minor depression.

A clinical and biological validation of the DSM-III melancholia diagnosis in men: results of pattern recognition methods.

Pattern recognition methods were carried out on a sample of 80 depressed men, assessed by means of 14 items relevant to depressive symptomatology of the Structured Clinical Interview for DSM-III-R. 1985 edition (SCID). A cluster analysis generated two classes, which were described as a vital (n = 35) and a nonvital cluster (n = 45). Vital depressives were characterized by psychomotor disorders, loss of energy, cognitive disturbances, a distinct quality of mood, early morning awakening and nonreactivity (the "vital" symptoms). Our findings support the descriptive validity of the DSM-III melancholia diagnostic category, although the DSM-III criteria are too conservative and include nonrelevant symptoms (e.g., diurnal variation, anorexia-weight loss) whilst excluding some important items (e.g., loss of energy, cognitive disorders). Vital depressed men were significantly older, more severely depressed and they exhibited biological disturbances (abnormal dexamethasone suppression test, lower basal thyroid secreting hormone) as opposed to nonvital depressives. There are several arguments to support the possibility that both clusters constitute relevant stages in the overall severity of illness continuum, whilst showing qualitative differences with regard to the vital symptoms. In other words, both clusters are continuous categories within the overall severity of illness continuum and form discrete categories with regard to the vital symptoms. By merging the dimensional and categorical hypotheses, we were able to construct a new integrated threshold model: unipolar depression in men is probably a homogeneous disease with reference to overall severity of illness, but--as severity increases--vital symptoms emerge, grouping together into a distinct profile, i.e., vital depression.