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Diagnostic validity of basic symptoms.

Although the Bonn Scale for the Assessment of Basic Symptoms (BSABS) [13] has come into use in several European countries, its diagnostic validity has not yet been sufficiently examined. That is why we have assessed BSABS items on a sample of 243 consecutive admissions to the Department of Psychiatry at the RWTH University, Aachen, and 79 psychologically healthy persons. Then, a cluster analysis was calculated to identify the empirical item-grouping. Five well-interpretable BSABS subsyndromes were found. In addition, uni- and multivariate analyses were computed to evaluate the diagnostic validity of these subsyndromes. We were able to show that every BSABS subsyndrome separates at least schizophrenic, organic mental and affective disorders from personality, neurotic and substance-induced disorders, as well as from psychological health. Furthermore, the subsyndrome "information processing disturbances" differentiates between schizophrenic and organic mental disorders, on the one hand, and affective disorders, on the other, and additionally, the subsyndrome "interpersonal irritation" between schizophrenics and all other persons examined.

Adult↗

Routine psychiatric examinations guided by ICD-10 diagnostic checklists (International Diagnostic Checklists).

A systematic assessment of psychiatric diagnoses according to the new classification system ICD-10 can be guided and enhanced by the International Diagnostic Checklists (IDCL). This instrument was developed and evaluated primarily for use in routine clinical care. It consists of 30 separate lists in pocket form, each assigned to a specific disorder and allowing immediate and operationalized diagnostic decisions (without the need of computer assistance). Personality disorders are covered by a separate 12-page booklet (IDCL-P). Examples of the checklists are given together with possible areas of application. First studies have indicated good clinical practicability and satisfactory to excellent diagnostic reliability.

Adult↗

Survey of cases of familial mental illness. L. S. Penrose, July 1945.

An investigation was made of all known cases of mental illness where more than one member of the family entered one of the Ontario Mental Hospitals. The materials is fairly complete for a period of 18 years. Analysis of the resulting data, on pairs of relatives, gave rise to the following conclusions of particular interest. (i) Schizophrenia, affective psychosis, senile psychosis, Huntington's chorea and mental defect are shown to be conditions which remain significantly true to type when mental disease occurs in different members of a family. As a rider to this, however, it is found that schizophrenia and affective psychosis are not very distinct entities and groups of closely related familial cases frequently include both diagnoses. (ii) Schizophrenia is a rare diagnosis in the fathers of patients and occurs in only 8.7% of fathers, as opposed to the 30.7% in the whole sample of relatives: it is not so rare in mothers (24.5%). (iii) The most frequent type of relationship in pairs of patients is sister and sister: next in frequency is the type brother and brother, then brother and sister. Mother and son, mother and daughter, father and daughter and then father and sone come next in order. Less frequent are uncle and nephew or uncle and niece and, again less frequent, aunt and nephew or niece; grandparents and grandchildren were rarely found. (iv) Fathers, diagnosed schizophrenic or first admitted below the age of 35, have more psychotic sons than psychotic daughters, but the reverse is true for mothers in the same categories. (v) Fathers diagnosed as having affective illness or first admitted at the age of 35 or over have more psychotic daughters than psychotic sons, but the reverse is true for mothers in the same categories. (vi) Male subjects with either schizophrenic or affective diagnosis and in early- or late-onset age groups, have more psychotic brothers than psychotic sisters. Similarly, female subjects have more psychotic sisters than psychotic brothers. (vii) Each main diagnosis group has its characteristic first admission age. (viii) The first admission age is earlier in males than in females for schizophrenics, and later in males than in females for affective disorders. (ix) Study of first admission ages in families indicates that parents and, particularly, grandparents are much older than children and, particularly, grandchildren at first admission. This effect is not attributed to progressive degeneration. (x) Male subjects show a significantly wider scatter of first admission ages than do female subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

History, 20th Century↗

Emotional disturbances and their interaction with neuropsychological deficits.

The interaction and relationships between neuropsychological tests (which are principally oriented to intellectual and cognitive abilities) and tests of personality and emotional status are complex, but nevertheless important in the clinical assessment of brain-damaged persons. Are indications of emotional disturbances to be expected as a direct consequence of brain damage? If so, how can the indications of emotional disturbances be differentiated from results obtained with psychiatrically disturbed (non-brain-damaged) subjects? Some authors have presumed that emotional disturbances, such as depression, acute anxiety, etc., in their own right cause impaired performances on neuropsychological tests, whereas other authors have proposed that brain damage predisposes the individual to demonstrate evidence of emotional disturbances. If emotional disturbances cause impairment on neuropsychological tests, why is it that so many emotionally disturbed persons without brain damage tend to perform normally on neuropsychological tests? This review of relevant publications considers (1) different general approaches to these questions and their implications for neuropsychology, (2) evidence of differential sensitivity to brain damage of neuropsychological and emotional instruments, (3) the sensitivity and specificity of self-assessments and complaints of head-injured subjects, (4) MMPI findings among head-injured subjects and in interaction with neuropsychological measurements, and (5) principles and guidelines that may be of value in clinical application of findings reported in the literature.

Anxiety↗

[Stalking--from psychoterror to murder].

Stalking is a widespread phenomenon describing a pattern of intrusive and threatening behavior that leads to the victim's perception of being harrassed and rendered afraid. This paper summarizes relevant aspects of the current stalking concept and reviews its historical development. Furthermore, different typologies of stalking behavior, associated psychiatric diagnoses, frequency and demographic data, therapeutic approaches, and the psychomedical effect on victims are described and discussed. Stalking is not restricted to celebrities but can affect everybody. Members of the medical profession and other socially exposed people are especially potential victims of stalkers. Therefore, information on this topic is necessary in order to deal with it in a professional manner.

Aggression↗

[Role of the cytokine network in the CNS and psychiatric disorders].

There is a strong interrelationship between the immune system, the central nervous system and psychological processes that are suggested to play a pivotal role in the pathogenesis of psychiatric disorders. In schizophrenia and depression, activation of the immune system has been observed repeatedly. Cytokines play a key role in immune activation. They are actively transported into the CNS, but also released from activated glia cells. Cytokines activate glia cells in the CNS to produce other cytokines, and a cascade of cytokine effects may be initiated by this mechanisms. During the past few years, the influence of the cytokines on dopaminergic, noradrenergic and serotonergic neurotransmission and also on the hormones of the hypothalamus-pituitary-adrenal axis has been elucidated. It suggests a pivotal role in psychological processes and psychiatric disorders. For example, in schizophrenia the IL-2 cerebrospinal fluid concentration shows a stronger relationship to the relapse probability than catecholamine metabolites. Although the hypersecretion of IL-2 in schizophrenia and of IL-6 in depression are suggested to play key roles for these disorders, a specificity of certain cytokines for certain psychiatric disorders seems unlikely. Psychomotor, sleep and sickness behavior are influenced by IL-1, disturbances of memory and attention by IL-2, but also by TNF-alpha. From the distribution of cytokine receptors in the CNS conclusions can be drawn regarding the influence of cytokines on psychological processes. The finding that norepinephrine stimulates activated astrocytes to produce IL-6 implies that the cytokine cascade may be activated by neuronal processes under certain conditions. This can lead to a molecular biological explanation of the influences of stress on the immune system. Lastly, influences of the cytokines on blood-brain barrier disturbances and further consequences resulting from the role of the cytokine network in the CNS are discussed.

Blood-Brain Barrier↗

The neurodevelopmental price of survival in children with malignant brain tumours.

Increasing survival rates in malignant brain tumors treatment have directed attention to the side effects of long-term disease control. Nevertheless, although the treatment protocols are continuously remodelled, the quality of life of children surviving for a long time is still poor. The most severe sequelae are neurocognitive disorders, which are associated with neurobehavioural alterations. The last are partly derived directly from the lesion localisation and treatments, but are often reinforced by academic and social failure. The deleterious effect of radiotherapy (CRT) is very well documented and confirmed in all the studies. The radiation dose delivered according to the age has reduced, but not fully eliminated, the negative influence on mental functioning. Also the CRT hyperfractionation has reduced, but not cancelled, this cognitive negative impact. Intrathecal methotrexate per se is responsible for a severe cognitive impairment, which can be even more severe in association to CRT. Some surgical approaches have been responsible for postoperative behavioural disturbances. Serial neuropsychological and behavioural evaluations, which should also include the survivors' own perception of their quality of life, are badly needed. The results of these evaluations should be covariate with several factors (age, type of surgery, lesion site, hydrocephalus, complementary therapies) in an attempt to define interdisciplinary treatment protocols to maximise survival while minimising cognitive/behavioural deficits.

Brain Damage, Chronic↗

[Age-associated changes in the metabolism of vitamin B(12) and folic acid: prevalence, aetiopathogenesis and pathophysiological consequences].

The increasing number of older people is characteristic for most industrialised nations and implicates the known psychosocial and economic consequences. Therefore, an optimal nutrient supply that promotes continuing mental and physical well-being is particularly important. In this respect, vitamin B(12) and folic acid play a major role, since deficiency of both vitamins is associated with the pathogenesis of different diseases such as declining neurocognitive function and atherosclerotic lesions. Vitamin B(12) and folic acid act as coenzymes and show a close molecular interaction on the basis of the homocysteine metabolism. In addition to the serum concentrations of the vitamins, the metabolites homocysteine and methylmalonic acid are sensitive markers of cobalamin and folate status. Depending on the used marker, 3-60% of the elderly are classified as vitamin B(12) deficient and about 29% as folate deficient. Predominantly, this high prevalence of poor cobalamin status is caused by the increasing prevalence of atrophic gastritis type B, which occurs with a frequency of approximately 20-50% in elderly subjects. Atrophic gastritis results in declining gastric acid and pepsinogen secretion, and hence decreasing intestinal digestion and absorption of both B vitamins. This is the reason why an insufficient vitamin B(12) status in the elderly is rarely due to low dietary intake. In contrast, folic acid intake among elderly subjects is generally well below the recommended dietary reference values. Even moderately increased homocysteine levels or poor folate and vitamin B(12) status are associated with vascular disease and neurocognitive disorders. Results of a meta-analysis of prospective studies revealed that a 25% lower homocysteine level (about 3 micromol/L) was associated with an 11% lower ischemic heart disease risk and 19% lower stroke risk. It is still discussed, whether hyperhomocysteinemia is causally related to vascular disease or whether it is a consequence of atherosclerosis. Estimated risk reduction is based on cohort studies, not on clinical trials. Homocysteine initiates different proatherogenetic mechanisms such as the formation of reactive oxygen species and an enhanced fibrin synthesis. Supplementation of folic acid (0.5-5 mg/d) reduces the homocysteine concentration by 25%. Additional vitamin B(12) (0.5 mg/d) induces further reduction by 7%. In secondary prevention, supplementation already led to clinical improvements (reduction of restenosis rate and plaques). Depression, dementia, and mental impairment are often associated with folate and vitamin B(12) deficiency. The biochemical reason of this finding may be the importance of folic acid and vitamin B(12) for the transmethylation of neuroactive substances (myelin, neurotransmitters) which is impaired in vitamin deficiency ("hypomethylation hypothesis"). In recent years, there is increasing evidence for a role of folic acid in cancer prevention. As a molecular mechanism of a preventive effect of folic acid the hypomethylation of certain DNA sections in folate deficiency has been suggested. Since folate and vitamin B(12) intake and status are mostly insufficient in elderly subjects, a supplementation can generally be recommended.

Aged↗

Primitive reflexes in a case-control study of patients with advanced human immunodeficiency virus type 1.

This study estimated the frequency of nine primitive reflexes (PR) and assessed their possible clinical value in a group of patients with acquired immunodeficiency syndrome. We studied 78 patients with human inmunodeficiency type 1 (HIV-1) infection in WHO clinical stage 3 or 4 and 81 matched seronegative controls. All participants were examined using a standardized neurological examination and the Mini-Mental State Examination. Cognitive impairment and PR was found in 36% of patients but in none of the controls (P<0.0001; logistic regression odds ratio: 14.7). Overall, PR were 2-36 times more frequent in patients with HIV-1 infection. This association was stronger for the glabellar, snout, Rossolimo, and digital signs. At least two PR were observed in 92% of patients vs. 8% of controls (P<0.0001; 95% confidence interval: 68%-100%; logistic regression odds ratio: 10.8). These data support the association of PR with cognitive decline in patients with advanced HIV-1 infection without overt neurological disease. Larger follow-up studies with multivariate techniques are needed to identify which PRs are useful as indicators of HIV-1-associated cognitive/motor complex and minor neurocognitive disorders.

Acquired Immunodeficiency Syndrome↗

[Neuropsychiatric symptoms in palliative care].

Up to 80% of patients in palliative care suffer from neurological and/or psychiatric symptoms. For many of those symptoms, there are effective treatment options which should be known to the treating physician. The following article reviews clinical, etiological and diagnostic aspects as well as treatment options. For this, a systematic literature search is combined with clinical experience. Pure motor restlessness often is caused by aggravated physical symptoms. Delirium paradoxically often is reversible, even in the palliative setting, but may also be irreversible and a sign of impending death. Fear and depression must not be overlooked as they may effectively be treated. Suicidal ideation may be dealt with without transfer to a psychiatric ward. Physician assisted suicide is critically discussed.

Humans↗

Multivariate analysis of primitive reflexes in patients with human immunodeficiency virus type-1 infection and neurocognitive dysfunction.

To prove that primitive reflexes are independent markers of symptomatic human immunodeficiency virus type-1 (HIV-1) infection, a case-control study was carried out in a tertiary care, university teaching hospital. Thirty HIV-1-positive symptomatic cases, 30 seropositive asymptomatic controls and 30 HIV-1 seronegative controls consented to participate and were selected consecutively. A single examiner blinded to serostatus administered the Mini-Mental State Exam and a structured neurological exam to each participant. Up to 45% of cases had cognitive impairment. The occurrence of neurologic signs between seropositive cases and seropositive controls was similar, but the number of primitive reflexes was significantly higher in cases (P < 0.001). By multivariate discriminant analysis, all primitive reflexes but two correctly classified 83.3% of all participants (P = 0.0013). The model had a positive predictive value of 97% when motor, mood, and cognitive symptoms were added (P = 0.0001). Primitive reflexes were independent predictors of HIV-1 serostatus, especially for those with cognitive dysfunction. Primitive reflexes should be included in future case definitions of HIV-1-related neurocognitive disorders.

AIDS Dementia Complex↗

Genetic evidence links hypertension to accelerated brain aging.

Hypertension affects one-third of adults and is a major comorbidity of neurocognitive disorders. The causal relationship, shared genetic architecture, and upstream mechanisms linking hypertension to brain aging remain unclear. Hypertension GWAS datasets from MVP and FinnGen R12 were meta-analyzed as the exposure, and a European-ancestry brain age gap (BAG) GWAS derived from the UK Biobank and LIFE-Adult cohorts was used as the outcome. MR and GSMR assessed causality. LDSC, HDL, and S-LDSC estimated genetic correlation. Four TWAS methods (MAGMA, FUSION, JTI-PrediXcan, FOCUS) mapped associations to genes, followed by SMR for causal validation and PoPS for prioritization. GSMAP with spatial transcriptomics characterized regional and cell-type enrichment. Hypertension and brain aging were genetically correlated, and MR and GSMR analyses suggested a causal effect of hypertension on increased brain age gap. TWAS identified 15 shared Hypertension-BAG genes, 10 supported by SMR. PoPS prioritized TRIM47 as the core gene. Shared signals were enriched in meninges, fiber tracts, cortical layer 1, and CA1 stratum lacunosum/radiatum, with cell-type enrichment in meninges, smooth muscle cells, oligodendrocytes, and astrocyte subtypes. Hypertension is genetically correlated with, and shows evidence of a causal effect on, accelerated brain aging. TRIM47 is a core gene bridging hypertension and BAG. GSMAP-based spatial enrichment provides a hypothesis-generating framework for understanding vascular, meningeal, and myelin-related pathways linking hypertension to increased brain age gap.

Humans↗

Common psychiatric syndromes and pharmacologic treatments of traumatic brain injury.

Psychiatric syndromes are common in patients with traumatic brain injury. Patients may develop typical disorders of mood, anxiety, or psychosis, in addition to changes in personality and cognition. The frequency of these syndromes and potential pharmacologic treatments for these psychiatric syndromes are just coming to light. There are, unfortunately, a dearth of placebo-controlled trials to guide treatment, although numerous treatments are suggested in the literature. This article reviews the existing studies of clinical syndromes related to brain injury and possible pharmacologic treatments.

Brain Injuries↗

Prevalence of partial cerebroside sulfate sulfatase (arylsulfatase A) defect in adult psychiatric patients.

Metachromatic leukodystrophy (MLD) is a disease caused by a deficiency of the enzyme sulfatide sulfatase, also known as arylsulfatase A (ASA). We compared the activity of this enzyme in adult psychiatric patients and normal volunteers using nitrocatechol sulfate (ASA-NCS) and cerebroside sulfate (ASA-CS) as substrates. Our results showed that ASA-NCS activity in urine and leukocytes was significantly lower in psychiatric than in normal individuals, but that there were no differences between these two groups in the sulfatide excretion in urine or the ASA-CS activity in leukocytes. There was no correlation between enzyme activity in urine and in leukocytes, indicating that activity in urine does not truly reflect the levels of the enzyme in tissues. The correlation between ASA-NCS and ASA-CS activity in leukocytes was poor (0.51 for psychiatric patients and 0.59 for normals), suggesting that for a valid measure of the enzyme activity the assays should be carried out with CS as substrate. Results of our study also indicate that in 39 of the 145 psychiatric patients studied, the ASA-CS activity in leukocyte was less than 4 nmoles/mg protein/hr, which is below 50% of the normal means, whereas only one of the 30 normal subjects had a value this low. The presence of low levels of ASA-CS activity in a significantly large number of adult patients with varying psychiatric manifestations suggests that such patients may be asymptomatic carriers of the sulfatidase defect (heterozygotes for MLD), and that behavioral and functional disturbances in these patients may at least in part be related to sulfatidase deficiency. The significance of the ASA-NCS abnormality (reduction) in psychiatric patients is unclear.

Cerebroside-Sulfatase↗

Is there gliosis in schizophrenia? Investigation of the temporal lobe.

Recent studies have described two indicators of pathology in the schizophrenic brain--gliosis and atrophy. The degree of gliosis in the temporal lobe of groups of schizophrenics (with demonstrable atrophy), affectives, and controls was quantified using immunocytochemical techniques and computer-assisted densitometry. Twenty areas within the temporal lobe were assessed. Our data showed no evidence of increased gliosis in the schizophrenic group compared to controls and affectives. This extends and replicates our previous findings, demonstrating that the atrophy/aplasia in schizophrenia is not associated with pathologically significant gliosis. Our observations are consistent with other studies, suggesting that the structural change in schizophrenic brains is due to an embryonic insult or developmental anomaly of an, as yet, undetermined nature.

Aged↗