In a double-blind, cross-over trial, triazolam (0.5 mg) was compared with nitrazepam (5 mg) in patients with disturbed sleep. Each drug was given once, with a 48-h interval, to 40 outpatients. Quality, duration, and latency of sleep, and number of awakenings during the night, showed a significant difference in favour of triazolam. An overall evaluation of sleep also showed triazolam to be superior to nitrazepam. Both drugs seemed to reduce dream activity and to alter the character of the dreams. There was no significant difference in side effects.
Sixty young male patients with insomniac disorders were treated with nitrazepam 5 mg or triazolam 0.5 mg in a double-blind single night cross-over study. The results were favourable for triazolam in all the sleep parameters assessed. The significance of an hypnotic with a short life and its use in clinical practice is discussed.
To examine the association between first hospital admissions due to postpartum psychosis and the explanatory variables age, educational level, marital status and year of delivery.
All Swedish first-time mothers (n = 502,767) were included during a 12-year period and followed for first hospital admissions due to postpartum psychosis. Cox regression was used to estimate hazard ratios, adjusted for the explanatory variables.
Older age and being a single mother implied an increased risk of first hospital admissions due to postpartum psychosis among first-time mothers. Educational level was not associated with first hospital admissions due to postpartum psychosis. During the 1990s, when a reduction in psychiatric beds occurred, first hospital admissions due to postpartum psychosis decreased significantly.
Certain sociodemographic factors are associated with first hospital admissions due to postpartum psychosis. Untreated postpartum psychosis due to fewer psychiatric beds could have hazardous effects on mothers and their children.
Zimelidine, a bicyclic compound, which in animal experiments causes specific inhibition of the uptake of 5-HT, was tried on 15 patients with depression of endogenous type. It produced considerable and highly significant 5-HT uptake inhibition in rat brain slices incubated in blood plasma from the patient under treatment, but no inhibition of NA uptake.
Depressive symptoms were effectively relieved or entirely abolished in about two thirds of the patients. Only four patients did not react to the drug, and three of these were probably in need of NA uptake inhibitors, which on other occasions had worked well on their depressions. These three patients showed an extreme degree of retardation. During zimelidine treatment they were not just unaffected but showed signs of excitation, impatience and desperate feelings. These preliminary findings strongly indicate the true existence of depressive cases in need of an NA uptake inhibitor, but completely resistant to a specific 5-HT uptake inhibitor.
The final dose of zimelidine was 75 mg b.i.d. This dose, although sufficient in most cases, was obviously somewhat low for a few of our patients. The concentration in blood plasma of zimelidine should probably reach a minimum level of 250 nmol/l and norzimelidine 500 nmol/l, and to achieve this a general dosage of 100 mg b.i.d. is recommended.
The severity of postpartum psychosis calls for further research on the association between obstetric variables and this psychiatric disorder.
A total of 1,133368 Swedish first-time mothers were included during a 29-year period yielding 1413 hospitalized cases of postpartum psychosis. Several obstetric variables were analysed separately after adjustment for possible confounders.
Respiratory disorder in the neonate, severe birth asphyxia, preterm birth, caesarean section, perinatal death and SGA infant were associated with an increased risk of postpartum psychosis. After adjustment for previous hospitalization for psychiatric disorder only preterm birth and acute caesarean section remained significant risk factors for postpartum psychosis (relative risks were 1.20 and 1.31 respectively). The relative risk of postpartum psychosis among first-time mothers with previous hospitalization for psychiatric disorder was increased more than 100-fold.
Careful clinical risk assessments of postpartum psychosis are crucial among women with a history of psychiatric disorder whereas obstetric variables have a minor importance.
To investigate seasonal and regional effects on bipolar I and II patients.
The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) patients were prospectively examined for monthly change in prevalence rates of depressed and recovered clinical status over the year. General Estimating Equation modeling was used to assess the effect of season on prevalence rates. Additionally, patients were stratified by bipolar subtype and by region.
A significantly higher prevalence rate of depression is observed in the northern sites, a significant prevalence by month effect is found only in the bipolar II patients.
The prevalence of depression is greater in patients from the northern vs. southern STEP-BD sites. Seasonal peak prevalence rates of depression differ by region. Bipolar II patients were more ill year-round and demonstrated greater monthly fluctuation in prevalence rates of being ill than did bipolar I patients. We conclude that seasonal effects upon bipolar patients vary by region and bipolar subtype.
Lifetime and 12-month prevalence of traumatic events and DSM-IV post-traumatic stress disorder as well as risk factors and comorbidity patterns were investigated in a representative community sample (n = 3021, aged 14-24 years).
Traumatic events and PTSD were assessed with the Munich Composite International Diagnostic Interview (CIDI).
Although 26% of male subjects and 17.7% of female subjects reported at least one traumatic event, only a few qualified for a full PTSD diagnosis (1% of males and 2.2% of females). Traumatic events and PTSD were strongly associated with all other mental disorders examined. PTSD occurred as both a primary and a secondary disorder.
The prevalence of PTSD in this young German sample is considerably lower than reported in previous US studies. However, the conditional probability for PTSD after experiencing traumas, risk factors and comorbidity patterns are quite similar. Traumatic events and full PTSD may increase the risk for other disorders, and vice versa.
We compared the prevalence and age of onset of adult and childhood anxiety disorders relative to the primary diagnosis in 68 women with anorexia nervosa (AN), 116 women with bulimia nervosa (BN), 56 women with major depression with no eating disorder (MD) and 98 randomly selected controls (RC) in order to determine whether antecedent anxiety disorders are plausible risk factors for AN and BN. Comorbid anxiety disorders were common in all three clinical groups (AN, 60%; BN, 57%; MD, 48%). In 90% of AN women, 94% of BN women and 71% of MD women, anxiety disorders preceded the current primary condition (P = 0.01), although panic disorder tended to develop after the onset of AN, BN or MD. In multivariate logistic regressions, the odds ratios (ORs) for overanxious disorder (OR = 13.4) and obsessive-compulsive disorder (OR = 11.8) were significantly elevated for AN. The ORs for overanxious disorder and social phobia were significantly elevated for BN (OROAD = 4.9; ORSP = 15.5) and MD (OROAD = 6.1; ORSP = 6.4). These data suggest that certain anxiety disorders are non-specific risk factors for later affective and eating disorders, and others may represent more specific antecedent risk factors.
To assess, in depressed patients, the clinical benefit of mianserin augmentation of fluoxetine or the the benefit of switching treatment from fluoxetine to mianserin.
In a 6-week double-blind study we compared the therapeutic efficiency and tolerance of mianserin 60 mg/day (N = 34), mianserin 60 mg/day plus fluoxetine 20 mg/day (N = 32) and continuing fluoxetine 20 mg/day (N = 38) in patients with major depression who did not respond to previous fluoxetine treatment.
Intent-to-treat analysis showed that at week 6 the decrease in the Hamilton Depression rating scale score was significantly (P < or = 0.03) greater in the mianserin plus fluoxetine group when compared to the fluoxetine group (effect size 0.665). Switching from fluoxetine to mianserin gave intermediate results. Mianserin augmentation of fluoxetine was well tolerated.
Mianserin augmentation of fluoxetine in patients non-responders to fluoxetine 20 mg/day increases response to treatment and is well tolerated.
Twelve hundred and six psychiatric in-patients, 506 men and 700 women, with severe depression/melancholia were rated at discharge with a multi-dimensional diagnostic schedule during 1956-1969. The sample was followed up until December 31, 1983. A total of 476 deaths were recorded including 103 suicides. Suicides and to a small proportion diseases of the nervous system constituted the total excess mortality in unipolar disorders. In bipolar disorders there was also an increased mortality from physical disorders, while the suicide frequency was lower (9% versus 4%). Male suicides had higher initial ratings for the items brittle, sensitive, marital problems, acute onset and lower ratings for psychomotor retardation than other men. Female suicides had a higher frequency of attempted suicides than other women. Acute onset and attempted suicide were associated with suicides early in the course contrary to the other differentiating items. The suicide frequency was similar in admissions during 1956-1962 compared with those during 1963-1969.
Whether responses to antidepressants differ in bipolar and unipolar depression remains unresolved.
We analyzed patient characteristics and outcomes of antidepressant treatment of 1036 depressed patients with bipolar-I or bipolar-II disorder, or unipolar major depression, using bivariate and multivariate methods and survival analysis, testing the hypothesis that responses would be superior in unipolar depression.
Antidepressants were given to 84.8% (878/1036) of depressed patients: 58.9% of 93 bipolar-I, 80.1% of 117 bipolar-II, and 91.3% of 668 unipolar disorder cases. The 158 not given antidepressants had more manias/year, spent more months in mania and depression, and were far more likely to receive mood stabilizers or antipsychotics long term. Improvement of HDRS21 depression ratings ranked: bipolar-II (69.6%) > bipolar-I (62.9%) > unipolar (57.9%; P < 0.0001), independent of initial illness severity. Responder rates (≥50% improved without switching) ranked: bipolar-II (77.0%) > bipolar-I (71.6%) > unipolar (61.7%; P < 0.0001). Remission rates (final HDRS < 7) ranked: 54.0%, 50.6%, and 40.8% respectively (P = 0.02); 67.5% remitted within 12 weeks of treatment. Survival-computed median time to remission (15.0 weeks, overall) was shortest for bipolar-II patients (10.7 weeks). The 3-month risk of switching into mania-hypomania ranked: bipolar-II (15.8%) > bipolar-I (8.60%) > unipolar (0.56%). Multivariate modeling found bipolar diagnosis, shorter latency to remission, more recent trial year, and fewer weeks depressed before treatment to be associated with greater percent improvement of HDRS ratings.
Selective use of antidepressants with or without mood stabilizers in non-agitated, depressed bipolar disorder patients for short periods was effective with moderate risk of potentially dangerous, manic mood elevation.
To provide a clinically useful analysis of the relationship between selective serotonin reuptake inhibitors (SSRIs), in particular fluoxetine and violent or suicidal behaviour.
All published papers on Medline and other databases linking serotonin, SSRIs and aggression were reviewed.
A small proportion of patients treated with SSRIs may become akathisic and others may show increases in anxiety in the initial phase of treatment, but no increased susceptibility to aggression or suicidality can be connected with fluoxetine or any other SSRI. In fact SSRI treatment may reduce aggression, probably due to positive effects on the serotonergic dysfunction that is implicated in aggressive behaviour directed towards oneself or others.
In the absence of convincing evidence to link SSRIs causally to violence and suicide, the recent lay media reports are potentially dangerous, unnecessarily increasing the concerns of depressed patients who are prescribed antidepressants.
Over recent years transcranial magnetic stimulation (TMS) has become widely applied in the study of neuropsychiatric disorders. The aim of this article is to review the application of TMS as an investigative tool and as a potential therapeutic modality in psychiatric disorders.
A comprehensive literature review.
When applied as an investigative tool, TMS provides innovative ways to directly study the excitability of the cortex, cortical regional connectivity, the plasticity of brain responses and cognitive functioning in illness and disease states. A number of studies suggest the potential of treatment with TMS in disease states, especially in patients with depression, although difficulties exist with the interpretation of the published literature.
TMS has a considerable role in neuropsychiatric research. It appears to have considerable potential as a therapeutic tool in depression, and perhaps a role in several other disorders, although widespread application requires larger trials and establishment of sustained response.
The relatively small number of male anorexia nervosa patients is often used as an excuse for the scarce literature on this subject. An exhaustive review of the literature (1970 to 1980), searching for case reports, yielded information about 107 males described as having anorexia nervosa. According to current criteria, the diagnosis was well documented in 37 patients. Data on the clinical picture and the social background were analysed and compared with a sample of 148 female anorectics. It was found that from the clinical point of view anorexia nervosa is strikingly similar in both sexes. A cluster analysis revealed that three subgroups might be distinguished in male cases: a '(pre)pubertal' variant, a 'lower class', and a 'middle class' variant. It is concluded that male patients should be involved in any future research on this syndrome.
To consider the impact of age and gender on the antidepressant response to nortriptyline and fluoxetine in melancholic depression.
Of 191 depressed patients, 113 met study criteria for melancholia. All patients were randomized to receive either fluoxetine or nortriptyline. Response rates, defined as an improvement of 60% or more on the Montgomery Asberg Depression Rating Scale over 6 weeks of antidepressant treatment on an intention to treat basis, were examined by age, and by age and gender.
Melancholic depressed patients 40 years or older, especially men, had a markedly superior response to nortriptyline compared with fluoxetine. Conversely, melancholic depressed patients, age 18-24 years, especially women, had a markedly superior response to fluoxetine.
Age and gender appear to be critical variables in understanding differential antidepressant responses to tricyclic antidepressants and selective serotonin reuptake inhibitors in melancholic depression.
To investigate the rate of impulse control disorders among pathological gamblers and examine the relationship of comorbidity to gambling severity.
Ninety-six adult pathological gamblers [mean age: 46.7 +/- 11.0 years; female: 44 (45.8%)] completed the following: Minnesota Impulsive Disorders Interview, Yale-Brown Obsessive-Compulsive Scale Modified for Pathological Gambling, and Gambling Symptom Assessment Scale.
Twenty-two subjects (22.9%) reported a comorbid impulse control disorder, most commonly compulsive sexual behaviour and compulsive buying. Subjects with comorbidity reported significantly greater intensity of urges (t = -2.021; df = 94; P = 0.046) and thoughts (t = -2.147; df = 42.3; P = 0.038) related to gambling, and greater interference (t = -3.913; df = 48.1; P < 0.001) and distress (t = -2.504; df = 52.7; P = 0.015) secondary to gambling urges and thoughts.
Impulse control disorders appear common among pathological gamblers and are associated with more severe gambling symptoms.
In a cohort of subjects with no history of psychopathology, we determined a 3-year incidence and the risk factors of comorbid and pure mood, anxiety and substance use disorders.
Data were obtained from the Netherlands Mental Health Survey and Incidence Study (NEMESIS), a longitudinal community study in which 4796 adults were interviewed in 1996, 1997 and 1999 with the Composite International Diagnostic Interview.
Of 2869 cases at risk, 10.8% developed an incident disorder within 3 years, of which 16.1% was comorbid. Neuroticism, childhood trauma and parental psychiatric history were more strongly associated with comorbid than with pure disorders. No differences emerged in events occurring in the first year after baseline, but events in the period thereafter showed markedly stronger associations with comorbidity and pure mood disorder than with pure anxiety and substance use disorder. Functional disability was also linked more strongly to comorbidity and pure mood disorder.
Clear risk factors exist for the rapid onset of comorbidity. Interventions are needed to prevent rapid comorbidity in subjects who recently developed a primary disorder.
The urinary excretion rates of norepinephrine were assayed in 26 patients diagnosed as major depressive disorders (primary, unipolar), before and after 14 days of treatment with the monoamine oxidase inhibitor Moclobemide (Ro 11-1163). A standardized 1-h urine collection procedure was used and norepinephrine was assayed by liquid chromatography with electrochemical detection. Norepinephrine was found significantly increased in depressed patients when compared with a control population. The psychotic patients showed the highest excretion rates although they were not significantly different from the endogenous (non-psychotic) group. Urinary norepinephrine output significantly decreased after 14 days of treatment with Moclobemide. This decrease was also marked in those patients that did not show any therapeutic effect. A clear antidepressant effect, shown by a significant decrease of the Hamilton Scale scores for depression, was apparent as early as the 7th day. Increased norepinephrine in melancholic patients was taken as a presumptive indication of altered sympathetic activity.
This study sought to examine the age-dependent persistence of attention deficit hyperactivity disorder (ADHD) and its predictors in a large sample of girls with and without ADHD followed prospectively for 11 years into young adulthood.
Participants were girls with (N=96) and without (N=91) ADHD and were 6-17 years old at the baseline assessment (mean age, 11 years) and 15-30 years old at the follow-up assessment (mean: 22 years). Participants were comprehensively and blindly assessed with structured diagnostic interviews and assessments of cognitive, social, school, and family functioning.
At the 11-year follow-up, 33.3% met full criteria for ADHD, 29.2% showed partial persistence of the disorder, 10.4% had impaired functioning, and 4.2% were remitted but treated (77.1% of the sample). Predictors of persistence were psychiatric comorbidity, family history of psychopathology, and family and school functioning at baseline.
These long-term, prospective, follow-up findings extend to girls findings that ADHD is persistent over the long term and can be predicted from psychosocial adversity and psychiatric comorbidity ascertained 11 years earlier.
Eleven beta-hydroxylase activity was assessed by measuring the cortisol to 11-deoxycortisol ratio in 20 control subjects, 38 patients with major depression, and five patients with Cushing's disease before and after 1 mg of dexamethasone. The mean levels of 11 beta-hydroxylase activity did not differ among groups before dexamethasone. After dexamethasone patients with Cushing's disease showed a nonsignificant increase in 11 beta-hydroxylase activity while patients with major depression and controls subjects both showed a decrease. Endogenous depressive patients were no more likely to show high 11 beta-hydroxylase activity than neurotic depressive patients; however, depressed patients with cortisol nonsuppression after dexamethasone were. Post-dexamethasone 11 beta-hydroxylase activity is positively correlated with age in both control subjects and patients with depression.
For psychiatric diagnoses, solving the problem of false positives is thought to be a matter of tightening diagnostic criteria. But low prevalence illnesses by their nature have high false positive rates. A recent study of bipolar disorder found the predictive value of bipolar diagnoses to be <50%. Is it possible to achieve much higher diagnostic accuracy for psychiatric diagnoses?
We calculate predictive values while varying diagnostic sensitivity and holding specificity constant, and vice versa, for a given prevalence of illness. We then calculate predictive values while holding sensitivity and specificity constant, but varying prior probability (clinically feasible by assessing other factors associated with bipolar outcomes, such as family history and degree of recurrence).
Assuming a sample in which the prevalence of illness is 10%, achieving positive predictive values (PPV) >50% requires diagnostic specificity of >95%. Holding specificity at a level already achieved clinically (86%), increasing prior probability yields predictive values as high as 83%.
Systematic assessment of clinical factors that increase the prior probability of illness, before applying DSM/ICD criteria, could raise PPV substantially compared with targeting greater specificity via more stringent diagnostic criteria.
The dexamethasone suppression test based upon analysis of 11-deoxycorticosterone, corticosterone and cortisol was applied to 20 female depressed patients (10 endogenous, 10 neurotic) and 10 healthy controls. Calculating ratios of corticosterone to its biological precursor 11-deoxycorticosterone allows to assess the activity of adrenal 11 beta-hydroxylase. This enzyme activity depends on the mean secretion rate of ACTH. The preliminary data indicate that the sensitivity of the test may be increased when based on this enzyme activity rather than upon plasma cortisol concentrations. The decrease of 11-deoxycorticosterone, a potent mineralocorticoid in relation to corticosterone may contribute to the reduced urine concentrating capacity in patients with endogenous depression.
Japan was the first country to abandon the 19th century term of 'mind-splitting disease' (schizophrenia). Revisions of DSM and ICD are forthcoming. Should the rest of the world follow Japan's example?
A comprehensive literature search was carried out in order to review the scientific evidence for the validity, usefulness and acceptability of current concepts of psychotic disorder.
The discussion about re-classifying and renaming schizophrenia and other psychotic disorders is clouded by conceptual confusion. First, it is often misunderstood as a misguided attempt to change societal stigma instead of an attempt to change iatrogenic stigma occasioned by the use of misleading and mystifying terminology. Second, the debate is misunderstood as purely semantic, whereas in actual fact it is about the core concepts underlying psychiatric nosology. Third, it has been suggested that the debate is political. However, solid scientific evidence pointing to the absence of nosological validity of diagnostic categories lies at the heart of the argument. Fourth, there is confusion about what constitutes a syndrome (a group of symptom dimensions that cluster in different combinations in different people and for which one or more underlying diseases may or may not be found) and a disease (a nosologically valid entity with specific causes, symptoms, treatment and course).
Scientific evidence favours a syndromal system of classification combining categorical and dimensional representations of psychosis. The concept of 'salience' has the potential to make the public recognize psychosis as relating to an aspect of human mentation and experience that is universal. It is proposed to introduce, analogous to the functional-descriptive term 'Metabolic syndrome', the diagnosis of 'Salience syndrome' to replace all current diagnostic categories of psychotic disorders. Within Salience syndrome, three subcategories may be identified, based on scientific evidence of relatively valid and specific contrasts, named Salience syndrome with affective expression, Salience syndrome with developmental expression and Salience syndrome not otherwise specified.
Hypofrontality is not a well-replicated finding in schizophrenia either at rest or under conditions of task activation.
Studies comparing whole brain and frontal blood flow/metabolism in schizophrenic patients and normal controls were pooled. Voxel-based studies were also combined to examine the pattern of prefrontal activation in schizophrenia.
Whole brain flow/metabolism was reduced in schizophrenia to only a small extent. Resting and activation frontal flow/metabolism were both reduced with a medium effect size. Duration of illness significantly moderated resting hypofrontality, but the moderating effects of neuroleptic treatment were consistent with an influence on global flow/metabolism only. Pooling of voxel-based studies did not suggest an abnormal pattern of activation in schizophrenia.
Meta-analysis supports resting hypofrontality in schizophrenia. Task-activated hypofrontality is also supported, but there is little from voxel-based studies to suggest that this is associated with an altered pattern of regional functional architecture.
To review the research addressing the relationship of childhood trauma to psychosis and schizophrenia, and to discuss the theoretical and clinical implications.
Relevant studies and previous review papers were identified via computer literature searches.
Symptoms considered indicative of psychosis and schizophrenia, particularly hallucinations, are at least as strongly related to childhood abuse and neglect as many other mental health problems. Recent large-scale general population studies indicate the relationship is a causal one, with a dose-effect.
Several psychological and biological mechanisms by which childhood trauma increases risk for psychosis merit attention. Integration of these different levels of analysis may stimulate a more genuinely integrated bio-psycho-social model of psychosis than currently prevails. Clinical implications include the need for staff training in asking about abuse and the need to offer appropriate psychosocial treatments to patients who have been abused or neglected as children. Prevention issues are also identified.
Population stratification, secondary effects of illness or treatment, biological heterogeneity of a clinical syndrome, or complex biology underlying a syndrome (where only one component is measured) are conditions which may obscure the association of a genetic risk factor with a clinical syndrome. We consider several investigative strategies under each of these conditions. Only segregation-based paradigms are robust to genetic heterogeneity and population stratification. But secondary effects on the risk factor produced by illness or treatment require other strategies for their detection.
The corpus callosum (CC) plays a pivotal role in inter-hemispheric transfer and integration of information and is a relatively understudied structure in bipolar disorder (BD). Magnetic resonance imaging (MRI) studies have reported callosal abnormalities in this condition but findings have been inconsistent. Structural changes affecting the CC may underlie functional abnormalities in BD and could contribute to, or explain the pathophysiology of, the condition.
A systematic review was carried out to identify, appraise and summarize MRI studies which compared callosal areas in BD with an unrelated control group. The findings were then synthesized using random effects meta-analysis. Consideration was given to a number of variables to explain heterogeneity.
Five case-control studies were identified. Bipolar patients showed reduced callosal areas in comparison with healthy volunteers with no evidence of heterogeneity or publication bias.
Findings from this study indicate that callosal areas are reduced in BD and suggest that a failure to integrate information across the hemispheres may contribute to the pathophysiology of the disorder. Further research is necessary to clarify the underlying cellular changes leading to these morphometric differences.
To reveal the EEG correlates of resting hypofrontality in schizophrenia (SZ).
We analyzed the whole-head EEG topography in 14 patients compared to 14 matched controls by applying a new parameterization of the multichannel EEG. We used a combination of power measures tuned for regional surface mapping with power measures that allow evaluation of global effects.
The SZ-related EEG abnormalities include i) a global decrease in absolute EEG power robustly manifested in the alpha and beta frequency bands, and ii) a relative increase in the alpha power over the prefrontal brain regions against its reduction over the posterior regions. In the alpha band both effects are linked to the SZ symptoms measured with Positive and Negative Symptom Scales and to chronicity.
As alpha activity is related to regional deactivation, our findings support the concept of hypofrontality in SZ and expose the alpha rhythm as a sensitive indicator of it.
To provide an overview for practicing clinicians on the pharmacological basis of cardiometabolic risk induced by antipsychotic drugs in patients with serious mental illness, to propose hypotheses to explain these risks and to give tips for managing cardiometabolic risk during antipsychotic treatment.
A MEDLINE search using terms for atypical antipsychotics (including individual drug names), metabolic, cardiovascular, weight gain and insulin resistance, cross-referenced with schizophrenia was performed on articles published between 1990 and May 2008.
Strong evidence exists for significant cardiometabolic risk differences among several antipsychotic agents. Histamine H1 and serotonin 5HT2C antagonism are associated with risk of weight gain, but receptor targets for dyslipidemia and insulin resistance have not yet been identified. Convincing data indicate that hypertriglyceridemia and insulin resistance may occur in the absence of weight gain with certain antipsychotics.
Although lifestyle and genetics may contribute independent risks of cardiometabolic dysfunction in schizophrenia and other serious mental illness, antipsychotic treatment also represents an important contributor to risk of cardiometabolic dysfunction, particularly for certain drugs and for vulnerable patients. Mental health professionals must learn to recognize the clinical signposts indicating antipsychotic-related cardiometabolic problems to forestall progression to type II diabetes, cardiovascular events and premature death.
The precursor of serotonin, L-5-hydroxytryptophan (L-5-HTP), was radiolabelled with 11C in the beta-position, yielding [beta-11C]serotonin after decarboxylation, allowing positron emission tomography studies of L-5-HTP uptake across the blood-brain barrier. We studied 8 healthy volunteers and 6 patients with histories of DSM-III major depression, 2 with repeated examinations after clinically successful treatment. We report a significantly lower uptake of [11C]5-HTP across the blood-brain barrier in depressed patients, irrespective of phase of illness. The findings emphasize that serotonin is involved in depressive pathophysiology and support earlier suggestions that the transport of 5-HTP across the blood-brain barrier is compromised in major depression.
We estimated the heritability for inpatient psychiatric treatment, treatment with psychoactive medication, and for psychiatric diagnoses in a randomized sample of 12,884 Swedish twin pairs drawn from the general population for a health survey. We found a genetic contribution to treatment and diagnosis, independent of sex and shared environment. The heritability estimate for inpatient treatment was 0.47, for reported treatment with psychoactive medication 0.49, and for an inpatient diagnosis of neurotic or personality disorder 0.60. No statistically significant heritability was found for the diagnoses of alcohol abuse nor for the heterogeneous group of diagnoses of psychoses. This was probably because of the heterogeneity of cases necessary to form large enough groups for analysis, or ascertainment requiring treatment in a psychiatric unit.
To describe structural and biochemical evidence from postmortem brains that implicates the reciprocal connections between the mediodorsal thalamic nucleus and the prefrontal cortex in cognitive symptoms of schizophrenia.
The estimation of the regional volumes and cell numbers was obtained using stereological methods. The biochemical analyses of molecular expression in postmortem brain involve quantitative measurement of transcripts and proteins by in-situ (RNA) or Western blot/autoradiography in brains from patients with schizophrenia and comparison subjects.
Stereological studies in postmortem brain from patients with schizophrenia have reported divergent and often opposing findings in the total number of neurons and volume of the mediodorsal (MD) thalamic nucleus, and to a lesser degree in its reciprocally associated areas of the prefrontal cortex. Similarly, quantitative molecular postmortem studies have found large inter-subject and between-study variance at both the transcript and protein levels for receptors and their interacting molecules of several neurotransmitter systems in these interconnected anatomical regions. Combined, large variation in stereological and molecular studies indicates a complex and heterogeneous involvement of the MD thalamic-prefrontal loop in schizophrenia.
Based on a considerable heterogeneity in patients suffering from schizophrenia, large variation in postmortem studies, including stereological and molecular postmortem studies of the MD thalamus and frontal cortex, might be expected and may in fact partly help to explain the variable endophenotypic traits associated with this severe psychiatric illness.
To determine continuities of mental health problems of children across a 24-year follow-up period.
In 1983, parent ratings of emotional and behavioral problems were collected with the Child Behavior Checklist (CBCL) in a general population sample of 2076 children. Twenty-four years later, 1365 participants completed Adult Self-Reports (ASR) to assess emotional and behavioral problems.
Of the participants who were classified as deviant in childhood, 22.2% were also classified as deviant in adulthood. Both homotypic and heterotypic continuity was found. Childhood aggressive, delinquent, and anxious/depressed problems were associated with most adult psychopathology. Attention problems did not predict later problems independently.
Even though assessed with parent-reports in childhood and analogous self-reports in adulthood, and over a large period of 24 years, continuity of psychopathology was found from childhood into adulthood. Anxious/depressed problems, delinquent behavior and aggressive behavior in childhood are core predictors for adult psychopathology.
An investigation material consisting of 120 persons who were born after refusal of an application for therapeutic abortion, with the same number of controls, has previously been followed up by the writers to the age of 21 years. This follow-up study has now been extended to completion of the 35th year. It is found that in social-psychiatric respects the index cases as a group are still somewhat worse situated than the control cases. However, the differences have to a certain extent levelled out and during the later part of the observation period no statistically significant differences can be demonstrated for any single variable.
This second follow-up study of 120 Swedish patients who were born between 1939-42 after refusal of therapeutic abortions extends the study to their 35th year. Individual information on economic support, criminal record, psychiatric care, health, and marriage/divorce was obtained from local social service authorities. Comparison was made with a 2nd control group. The results of the extended observation reveals a decrease in the differences between the 2 groups although the test group continues to show more frequent records of social and psychiatric difficulties. Over the extended period the differences have leveled out and no statistically significant differences can be demonstrated for any single variable.
The occurrence of comorbid attention-deficit hyperactivity disorder (ADHD) might have an impact of the course of the bipolar disorder.
Patients with bipolar disorder (n = 159) underwent a comprehensive evaluation with respect to affective symptoms. Independent psychiatrists assessed childhood and current ADHD, and an interview with a parent was undertaken.
The prevalence of adult ADHD was 16%. An additional 12% met the criteria for childhood ADHD without meeting criteria for adult ADHD. Both these groups had significantly earlier onset of their first affective episode, more frequent affective episodes (except manic episodes), and more interpersonal violence than the bipolar patients without a history of ADHD.
The fact that bipolar patients with a history of childhood ADHD have a different clinical outcome than the pure bipolar group, regardless of whether the ADHD symptoms remained in adulthood or not, suggests that it represent a distinct early-onset phenotype of bipolar disorder.
Schizophrenics with a neurodevelopmental disturbance resulting in micro- and macroanatomical cortical abnormalities are supposed to form a subgroup clinically characterized by low premorbid adjustment, early onset, incomplete remission, poor outcome, male predominance and high risk for tardive dyskinesia. A small amplitude of the event-related P3 (P300) potential could be a marker of this subgroup, because the cortical neurons and their orderly laminar arrangement are crucial for the electrogenesis of P3. In a 2-year follow-up study, auditory evoked P3 was recorded in 89 stabilized schizophrenic outpatients. Patients who developed tardive dyskinesia during the follow-up had smaller P3 than matched controls. Furthermore, a small P3 was associated with low premorbid adjustment, pronounced residual symptoms, low relapse rate, and male predominance. These findings indicate that schizophrenic patients with a reduced P3 have a higher risk of developing tardive dyskinesia and correspond clinically to a schizophrenic subgroup with a supposedly neurodevelopmental disturbance.
To investigate whether the lifetime number of affective episodes or illness duration is associated with changes in local grey matter volume, in patients with bipolar I disorder without comorbid conditions.
Magnetic resonance imaging scans of 55 patients with bipolar I disorder were analysed using VBM.
Smaller grey matter volume in the inferior frontal gyri of the dorsolateral prefrontal cortices (DLPFC) correlated significantly to the lifetime number of manic episodes. No association between local grey matter volume and the lifetime number of depression episodes or illness duration was found.
We found strong evidence for a linear correlation between a decrease in DLPFC volume and the lifetime number of manic episodes in patients with bipolar I disorder. Interestingly, DLPFC is known to be important for executive functions and the findings in this study might hence be linked to the executive cognitive deficits associated with bipolar disorder.
To investigate dopamine transporter binding in Gilles de la Tourette syndrome (GTS) with SPECT and [123I]FP-CIT.
Ten neuroleptic naïve/free patients with GTS, and 10 age- and gender-matched normal volunteers were studied. Subjects were clinically evaluated. GTS severity and affective symptoms were measured and the presence of GTS-related behaviours were recorded.
The GTS group showed significantly higher binding in both caudate and putamen nuclei than the controls. No associations were found between striatal binding ratios and measures of affect or GTS-related behaviours.
Patients with GTS show higher striatal binding of FP-CIT to the striatum in comparison with age- and gender-matched control subjects, indicating that dopamine transporter abnormalities are involved in the pathophysiology of GTS. These abnormalities appear to be distributed across both caudate and putamen.
Our study addressed two primary questions: (1) How reliable is long-term recall of lifetime history of episodes of depressed mood? (2) What characteristics are associated with consistent recall of this history?
Psychiatric symptoms were assessed in a population-based longitudinal survey of 1498 persons twice, in 1981 and 1994. Respondents whose reports of history of depressed affect were discordant after a 13-year follow-up interval were compared with those whose reports were concordant.
Absence of a reported history of episode of depressed mood was more consistently recalled than presence of such an episode. The kappa of reported lifetime history of episode of depressed mood was 0.32. Several personal characteristics predicted consistency of recall.
If assessment of past episodes of depressed mood is used as guide for identifying cases at risk for depression, account must be taken of the personal factors that might influence recall.
A community survey in metropolitan Taipei (MT) and two small towns (ST) by using the Chinese modified diagnostic interview schedule (DIS-CM) revealed a significant difference in the prevalence of alcohol abuse (AA) defined by DSM-III between two study samples (MT 3.4%; ST 8.0%), but the prevalence of alcohol dependence (AD) was not different (MT 1.5%; ST 1.8%). These figures are significantly higher than that of an earlier Formosan study. Demographic data, psychiatric symptoms, medical complications and impairment of social functions were adopted as the variables to validate the nosological status of AA and AD. The results of this study substantiated that AA and AD identified by the DIS-CM were nosologically different from a non-alcoholic group. The possible reasons for an increasing prevalence of alcoholism in Taiwan Chinese were discussed. An etiological hypothesis was proposed for AA and AD on account of their differential prevalences.
To describe the suicide rates of psychiatric in-patients in the canton of Zurich for the period 1992-2004, and to determine putative risk factors.
The data were derived from the psychiatric case register of the canton Zurich. The analyses were based on person-years calculations and standardised mortality ratios. Additional information was assessed via case records.
During the 13-year period the standardised mortality ratio was 48.9. The risk of suicide was particularly high in patients with personality and affective disorders. Most suicides occurred during regular leave periods, despite the fact that clinical assessment had indicated there was no suicide risk for the patient.
The suicide risk of in-patients is distinctly higher than in the general population. A better assessment of suicide risk before regular leave periods could lead to a decrease of suicides in in-patient settings, as well as a more rigorous treatment of borderline cases, and of affective and psychotic symptoms.
A retrospective study was performed to evaluate the effect of long-term treatment with clozapine in 96 schizophrenic or schizoaffective patients hospitalized at the Psychiatric Research Center in Uppsala during the period 1974-1986. All patients had previously been treated with different neuroleptics but with inadequate response or distressing side effects. The mean duration of the disorder at the start of clozapine treatment was 8 years and 9 months and the mean duration of the treatment 3 years and 11 months. Clozapine treatment was discontinued in 36% of the patients, mainly due to lack of efficacy, poor compliance or temporary withdrawal of the drug from the market in 1975. In two patients the reason was leukopenia or agranulocytosis. In another 10 patients a transient decrement of WBC was seen, which was normalized during ongoing treatment. Four patients died when on clozapine during the follow-up period, but no causal relationship to the treatment could be established. Eighty-five per cent of the patients could be discharged from the hospital. Of the 62 patients who were still on clozapine after 2 years, 18% had full time and 21% half-time employment. A global evaluation of the clinical efficacy revealed a significant improvement in 43% and a moderate improvement in 38% of the patients compared to previous neuroleptic treatments. Common but usually mild side effects were sedation, hypersalivation, weight gain, and obstipation. Four patients had grand mal seizures. No extrapyramidal side effects were observed during clozapine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Thirteen male-to-female transsexuals were investigated 6 to 25 years after surgery. Thirty-five prognostic items were compared with each of three outcome variables. Traumatic loss of both parents in infancy was connected with repentance at follow-up. A childhood family of an overprotective mother and a distant father, on the other hand, was prognostically favourable. Contrary to most previous reports, high sexual activity and bisexual experience was associated with fair sexual adjustment and with non-repentance after sex change. The repenting individuals, on the other hand, had been a-sexual or hyposexual before surgery. Completed military service, a history of typically masculine, hard jobs, and a comparatively late (more than 30 years of age) first request for surgery, were found to be negative prognostic factors in sex-reassignment evaluations. The phenomenon of ambivalence or hesitance during the trial period is discussed. Both too much and too little ambivalence may suggest a poor prognosis.
In Denmark about 11-12 per 100,000 population are diagnosed as schizophrenics for the first time each year. Less than half of these receive this diagnosis at first admission and therefore only 5-6 per 100,000 are included in the official schizophrenia incidence figures. In a cohort (n = 53), predictors for diagnosis of schizophrenia at the first admission were analysed (vs. first schizophrenia diagnosis only at a later admission). In accordance with the Danish concept of schizophrenia, affective flattening was found to have a significant correlation with the initial diagnosis of schizophrenia. Long duration of disease prior to the initial admission was also significantly correlated, indicating that a criterion of chronicity forms part of the Danish concept of schizophrenia. Schneider's first-rank symptoms also were more weakly correlated with the initial schizophrenia diagnosis. The probands were followed up personally and by case records (13 years). Good outcome was found in 23% of the probands and poor outcome in 50%. Affective flattening and Schneiderian first-rank symptoms at initial admission were correlated with poor outcome (NS). Schneiderian first-rank symptoms and social unease at initial admission were significantly correlated with schizophrenia as follow-up diagnosis. The initial clinical diagnosis of schizophrenia was not correlated with clinical outcome or with follow-up diagnosis.