Mental Health and Social Isolation Among Survivors Ten Years After a Suicide in the Family: A Case-Control Study

The aim of this study was to investigate mental health and social isolation in surviving family members (n=56) 10 years after a suicide as compared to sex and age matched general population controls. Minor mental disorders were more common among suicide survivors than among general population controls (30% vs. 16%), especially in surviving spouses (39% vs. 11%). Suicide survivors had fewer close friends than their controls. According to multivariate logistic regression analyses adjusted for several socioeconomic factors and the number of close friends, surviving spouses, but not relatives by blood, had a significantly increased risk of having minor mental disorder as compared to general population controls. Our conclusion is that suicide may be associated with mental symptoms and lack of social relationships in surviving spouses even 10 years later.     

Decreased CSF concentrations of homovanillic acid and gamma-aminobutyric acid in Alzheimer's disease. Age- or disease-related modifications?

Fifteen patients, 48 to 72 years old, with Alzheimer's disease were studied. Clinical status was assessed by neurologic and neuropsychologic examinations and psychometric testing. Patients were divided into two groups on the basis of clinical assessment: group 1, little mental deterioration, and group 2, serious mental deterioration. Nineteen subjects, 27 to 72 years old, without neurologic disease served as controls. Levels of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and gamma-aminobutyric acid (GABA) were determined in lumbar CSF by fluorimetric or radioreceptor binding (GABA) methods. The HVA concentrations increased with age in the controls, whereas the GABA levels decreased with age and 5-HIAA levels were not modified. When compared with the age-matched controls, the patients with Alzheimer's disease showed low concentrations of HVA but not of 5-HIAA or GABA. The decrease in HVA level was more pronounced in patients with severe mental deterioration and therefore appeared to be disease related.     

Platelet abnormalities in aggressive subjects with mental deficiency.

Platelet 3H-imipramine (3H-IMI) binding and platelet sulfotransferase (ST) activity, taken as markers of the serotonin (5-HT) and sulfated neurotransmitters (tyramine, dopamine, serotonin, noradrenaline), respectively, were evaluated in 14 severely aggressive subjects institutionalized since childhood for mental retardation and in an equal number of healthy controls. The results showed the presence of a lower number of 3H-IMI binding sites and a higher ST activity in the patients as compared with controls. These data provide supporting evidence for the hypothesis of an abnormality of the 5-HT system and suggest possible dysfunctions of dopamine and sulfated amines in aggressive behavior, at least as reflected by platelet markers.     

Peripheral-type benzodiazepine receptors in anxiety disorders.

Peripheral benzodiazepine receptors (pBDZr) were analyzed in lymphocyte membranes from patients with anxiety disorders (generalized anxiety disorder (GAD), n = 15; panic disorder (PD), n = 10; obsessive-compulsive disorder (OCD), n = 18), other mental disorders (n = 40) and 50 healthy controls, by the specific binding of 3H-PK11195. The number of binding sites (Bmax) was significantly decreased in groups with both GAD and OCD as compared with age-matched controls, by 45% and 25% respectively, whereas the binding affinity (Kd) was the same in all disorder and control groups. Conversely, no changes in binding capacity was observed in the other disorder groups and particularly in the one with PD. The abnormality in pBDZr observed in patients with GAD was restored to a normal value after long-term treatment with 2'-chloro-N-desmethyldiazepam, which also coincided with their recovery from anxiety. Our data suggest that the clinical heterogeneity in anxiety disorders might be related to different biological mechanisms and that lymphocyte pBDZr might be useful in demonstrating these differences.     

Apolipoprotein E is a genetic risk factor for fetal iodine deficiency disorder in China

Fetal iodine deficiency disorder (FIDD) is the principal form of endemic cretinism, and the most common cause of preventable mental deficiency in the world. However not everyone at risk develops FIDD and familial aggregation is common. This suggests that genetic factors may also be involved. The Apolipoprotein E (APOE) gene encodes for a lipoprotein that possesses a thyroid hormone binding domain, and APOE genotype may affect the efficiency with which thyroid hormone influences neuronal cell growth during the first and second trimesters of fetal development. We have compared ApoE genotypes in 91 FIDD cases with 154 local control subjects, recruited from three iodine deficiency areas in central China. We have also genotyped 42 FIDD family cases and 158 normal individuals from the families of local controls, and 375 population controls from Shanghai. APOE epsilon4 genotypes were significantly enriched in FIDD probands from each of the three iodine deficiency areas; the epsilon4 allele frequency was 16% vs 6% in controls. The same effect was also observed when we compared FIDD family cases with controls and control families. Our data suggest that in iodine-deficient areas, the APOE epsilon4 allele is a genetic risk factor for FIDD. The phenomenon may affect population selection and contribute to the low frequency of the epsilon4 allele in Chinese compared to Caucasian populations.     

Effects of L-beta-N-methylamino-L-alanine (L-BMAA) on the cortical cholinergic and glutamatergic systems of the rat.

Neurotoxic properties of L-beta-methylamino-alanine (L-BMAA) after chronic intracerebroventricular (i.c.v.) (500 micrograms/day) administration up to 60 days were investigated in the cerebral cortex of the rat. At day 16, there was a significant decrease in acetylcholinesterase (AChE) activity, 3H-QNB binding, 3H-glutamate (GLU) binding, and 3H-glutamate binding in the presence of quisqualate (QA). Choline acetyltransferase (ChAT) activity and 3H-nicotine binding were increased at day 16; however, ChAT activity decreased below control levels at days 40 and 60. 3H-Nicotine and 3H-AMPA binding were significantly lower than controls at both days 40 and 60. These significant neurochemical differences from unoperated controls were seen in both drug-injected and non-injected sides of the cortex suggesting a generalized cortical damage to glutamatergic and cholinergic systems. In the presence of bicarbonate, L-BMAA inhibited in vitro both glutamate and AMPA binding sites. L-BMAA treatment elicited behavioral changes such as splay, jerking movements, and rigidity. These symptoms were present for a period of at least 6 days after daily administration. After this period, symptoms were gradually attenuated and at day 10 the behavior of the L-BMAA-treated animals was not different from that of Na-bicarbonate injected controls. Our results are interpreted as an activation of quisqualate (AMPA) receptors by L-BMAA involving NMDA as well as non-NMDA receptors.     

Serum neurotrophin concentrations in autism and mental retardation: a pilot study

To evaluate the availability of the serum neurotrophins for the diagnosis of the patients with neurodevelopmental disorder, we measured the serum concentration of brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) in the patients diagnosed with autism (n=18) and mental retardation (n=20), or healthy controls (n=16), using enzyme-linked immunosorbent assay. There tended to be a higher concentration of serum BDNF found in the autistic group ( P <0.05 by analysis of variance (ANOVA)) and the mental retardation group ( P <0.001 by ANOVA) compared to the control group. Serum NT-4 concentration tended to be increased in the mental retardation group (P <0.05 by ANOVA). We conclude that measuring the serum concentration of two neurotrophins, BDNF and NT-4, might be helpful to diagnose or classify disorders such as autism or mental retardation.     

Brain GABAA/benzodiazepine binding sites and glutamic acid decarboxylase activity in depressed suicide victims

We have investigated the involvement of gamma-aminobutyric acid (GABA) in depression by quantitating benzodiazepine (BZ) binding sites, the ability of GABA to stimulate BZ binding and glutamic acid decarboxylase activity in frontal and temporal cortex obtained at postmortem examination from 21 suicide victims and 21 age- and sex-matched controls. We limited our study to suicide victims with clear evidence of depression, in the absence of symptoms of other psychiatric disorders. Thirteen of the depressed suicide victims had not been prescribed psychoactive drugs recently and none were found in their blood at postmortem; of the remaining 8 suicides, 6 were receiving antidepressant drugs, alone or in combination with other drugs. The number of BZ binding sites was significantly greater (by 18%) in the frontal cortex of the total group of depressed suicides compared to controls, but did not differ in the temporal cortex. The increase in the number of BZ binding sites in the frontal cortex was of similar magnitude when drug-free (16%), drug-treated (21%) and antidepressant-treated suicides (16%) were compared to matched controls, although the increase was only statistically significant for the drug-treated suicides. The Kd of BZ binding and the ability of GABA to stimulate BZ binding did not differ significantly between controls and the total, drug-free, drug-treated or antidepressant-treated suicides in either cortical area. Glutamic acid decarboxylase activity did not differ significantly between control and suicide groups, but was markedly reduced in subjects dying by carbon monoxide poisoning. The present study provides evidence for a greater number of BZ binding sites in the frontal cortex of depressed suicide victims, which could not clearly be attributed to drug treatment.     

Alpha-1- and 2-adrenoceptor subsensitivity in siblings of opioid addicts with personality disorders and depression

Noradrenergic receptor sensitivity of 16 healthy male siblings of heroin addicts and of 8 age and sex-matched controls was examined by administering a clonidine stimulation test and by measuring the resulting growth hormone (GH) (alpha-2-adrenoceptors) and beta-endorphin (β-endorphin) (alpha-1-adrenoceptors) responses. Siblings were divided into two groups: A = siblings of heroin addicts with personality disorders and high aggressivity and B = siblings of heroin addicts without mental disorders. The GH and β-endorphin responses to clonidine were blunted in group A subjects compared with controls and normal in group B.     

Different brain profiles in children with prenatal alcohol exposure with or without early adverse exposures

Prenatal alcohol exposure (PAE) can alter brain development and impact mental health outcomes, and often occurs in conjunction with postnatal adversity (e.g., maltreatment). However, it is unclear how postnatal adverse exposures may moderate mental health and brain outcomes in children with PAE. T1‐weighted and diffusion magnetic resonance imaging were obtained from 66 participants aged 7–16 years. Twenty‐one participants had PAE and adverse postnatal exposures (PAE+), 12 had PAE without adverse postnatal exposures (PAE?), and 33 were age‐ and gender‐matched controls unexposed to either prenatal alcohol or postnatal adversity. Internalizing and externalizing mental health symptoms were assessed using the Behavioral Assessment System for Children II, Parent‐Rating Scale. ANCOVAs were used to compare mental health symptoms, limbic and prefrontal cortical volumes, and diffusion parameters of cortico‐limbic white matter tracts between groups, and to assess brain‐mental health relationships. Both PAE groups had worse externalizing behavior (higher scores) than controls. The PAE? group had lower fractional anisotropy (FA) in the bilateral cingulum and left uncinate fasciculus, and smaller volumes in the left anterior cingulate cortex than controls and the PAE+ group. The PAE? group also had higher mean diffusivity (MD) in the left uncinate than the PAE+ group, and smaller right anterior cingulate and superior frontal gyrus volumes than controls. These findings show different brain structure and mental health symptom profiles in children with PAE with and without postnatal adversity, highlighting the need to consider adverse postnatal exposures in individuals with PAE.     

Platelet imipramine binding and serotonin uptake in obsessive-compulsive patients

Platelet imipramine binding was measured in 16 drug-free nondepressed patients (aged 20-61 years, mean ± SD 35 ± 8) suffering from obsessive-compulsive disorder (OCD) and in 16 sex-, race- and age-matched healthy controls. Imipramine binding capacity and affinity were not different in the 2 groups. Platelet serotonin (5-HT) uptake capacity, V_max, was also measured in 15 of these patients and their matched controls. V_max was significantly higher in the patients (309 ± 149 pmol/10⁹ cells/min) than in the controls (181 ± 110). An increase in platelet 5-HT uptake supports the involvement of 5-HT in OCD and may suggest that a hyperactive serotonergic system is present in this disorder.     

Neurochemical and neurotransmitter studies in patients with learning disabilities]

To clarify the pathophysiology of learning disability (LD), we measured the urinary levels of 3-methoxy-4-hydroxyphenyl glycol (MHPG), and phenylethylamine (PEA) in urine samples collected in a 24 hour period. Findings were compared with those obtained in age-matched controls and diseased controls including patients with attention deficit-hyperactivity disorder (ADHD), infantile autism, and mental retardation. The mean urinary level of MHPG in LD (n = 6) were not significantly different from those in ADHD (n = 16), mental retardation (n = 4), infantile autism (n = 5), and the controls (n = 6), while the mean urinary levels of PEA were significantly lower in LD (n = 6, 91 +/- 17.3 micrograms/mg) and in ADHD (n = 5, 65 +/- 53.6 micrograms/mg) as compared to age-matched controls (n = 3, 340 +/- 264.5 micrograms/mg) ANOVA, (p < 0.05). PEA is considered to play an important role for the pathogenesis of LD and ADHD.     

Binding of [3H]serotonin to lymphocytes in patients with neuropsychiatric disorders

Based on recent studies of neuroimmune networks, the lymphocyte binding of serotonin neurotransmitter was studied in patients with Alzheimer’s disease, idiopathic mental retardation, and autism. The specific binding to lymphocytes of [³H]serotonin, at a single concentration of 100 nM, was significantly reduced in Alzheimer’s disease patients as compared to aged controls (group mean of 3.667 ± 2.301 v 7.506 ± 1.717 picomoles;p=0.001), and in children with idiopathic mental retardation as compared to healthy children (group mean of 3.694±1.627 v 5.792±1.902 picomoles;p=0.003). However, autistic children did not differ significantly from the healthy children (group mean of 5.287±1.987 v 5.792±1.902 picomoles;p=0.475). Reduced lymphocyte binding of serotonin may be an indication of breakdown of an unknown neuroimmune pathway relevant to the pathophysiology of Alzheimer’s disease and idiopathic mental retardation.     

Levodopa-induced motor complications are associated with alterations of glutamate receptors in Parkinson's disease

Glutamate receptors were studied in the brains of controls and Parkinson's disease (PD) patients, of which 10 of 14 developed motor complications (dyskinesias and/or wearing-off) following levodopa therapy. (125)I-RTI binding to the dopamine transporter and dopamine concentrations show comparable nigrostriatal denervation between the subgroups of PD patients. (3)H-Ro 25-6981 binding to the NR1/NR2B NMDA receptor was increased in the putamen of PD patients experiencing motor complications compared to those who did not (+53%) and compared to controls (+18%) whereas binding remained unchanged in the caudate nucleus. (3)H-AMPA binding was increased in the lateral putamen (+23%) of PD patients with motor complications compared to those without whereas it was decreased in the caudate nucleus of the PD patients (-16%) compared to controls. Caudate and putamen (3)H-CGP39653 binding to NR1/NR2A NMDA receptor and NR1 subunit mRNA levels measured by in situ hybridization were unchanged in subgroups of PD patients compared to controls. These findings suggest that glutamate receptor supersensitivity in the putamen plays a role in the development of motor complications (both wearing-Off and dyskinesias) following long-term levodopa therapy in PD.     

Ethnicity as a risk factor for mental illness

This article shows the influence of ethnicity on mental health compared with material factors and lifestyle, which are well-known risk factors for mental illness. The study was designed as a case-control study, with 338 Latin American refugees aged 16–74 years (response rate = 81.8%) in Lund, and a random sample of 996 age-, sex- and education-matched Swedish controls. The data were analysed unmatched with logistic regression in main effect models. The strongest independent risk mediator for mental illness was ethnicity, with an estimated odds ratio of 4.11 (2.31–6.92). Low material standard was associated with mental illness, with an odds ratio of 2.13 (1.07–4.11). Individuals who did not feel secure in daily life were at risk of mental illness, as were those with poor leisure opportunities. The combination of ethnicity, age over 44, and not feeling secure in daily life increased the odds ratio of mental illness to 26.62. Ethnicity, a low material standard, not feeling secure in daily life and poor leisure opportunities were significant risk factors for mental illness. Dalby, Sweden     

Conditional Reasoning in Asperger's Syndrome and Depersonalization Disorder

ABSTRACT: Conditional reasoning premises can be systematically manipulated to elicit specific response patterns. This is useful for investigating the reasoning style of people who report clinical symptoms. We administered a standardized conditional reasoning task to 16 participants with a diagnosis of Asperger's syndrome (AS), 16 participants with a diagnosis of depersonalization disorder (DPD), and 32 intelligence-quotient-matched controls. Premises were manipulated for a) context, with some being embedded within extra statements, and b) content, neutral or emotional. Both the AS and DPD participants were less likely to incorporate exceptions to the given premises than the controls, indicating difficulties with mental flexibility, although this effect was less marked in the DPD group. It seems the AS participants were also less influenced than the controls by statements that highlight possible alternative consequences. However, this effect was less robust than that observed with statements detailing exceptions, suggesting it may be because of general problems with executive function rather than difficulties in processing contextual information. We did not observe the expected difference between the DPD participants and the controls when reasoning with emotional premises. Overall, these data suggest that the DPD and AS participants have distinct reasoning styles, which may be of use for interventions based on cognitive change.     

Mental retardation and memory for spatial locations

Although memory for spatial location has been frequently investigated with mentally retarded populations, it is not clear that these individuals possess the same spatial memory skills as do their peers without mental retardation. We compared 30 persons with and 30 persons without mental retardation. Following either intentional or incidental learning, participants recalled and then relocated 16 objects on a matrix. The control group recalled more intentionally learned than incidentally learned material. The experimental group performed both tasks better after incidental learning than after intentional learning and scored as highly as the controls on incidental spatial memory. Results suggest that memory for spatial location is an automatic process and, to some extent at least, is not directly affected by the individual's level of intelligence.     

Interference between postural control and mental task performance in patients with vestibular disorder and healthy controls

OBJECTIVES: To determine whether interference between postural control and mental task performance in patients with balance system impairment and healthy subjects is due to general capacity limitations, motor control interference, competition for spatial processing resources, or a combination of these. METHOD: Postural stability was assessed in 48 patients with vestibular disorder and 24 healthy controls while they were standing with eyes closed on (a) a stable and (b) a moving platform. Mental task performance was measured by accuracy and reaction time on mental tasks, comprising high and low load, spatial and non-spatial tasks. Interference between balancing and performing mental tasks was assessed by comparing baseline (single task) levels of sway and mental task performance with levels while concurrently balancing and carrying out mental tasks. RESULTS: As the balancing task increased in difficulty, reaction times on both low load mental tasks grew progressively longer and accuracy on both high load tasks declined in patients and controls. Postural sway was essentially unaffected by mental activity in patients and controls. CONCLUSIONS: It is unlikely that dual task interference between balancing and mental activity is due to competition for spatial processing resources, as levels of interference were similar in patients with vestibular disorder and healthy controls, and were also similar for spatial and non-spatial tasks. Moreover, the finding that accuracy declined on the high load tasks when balancing cannot be attributed to motor control interference, as no motor control processing is involved in maintaining accuracy of responses. Therefore, interference between mental activity and postural control can be attributed principally to general capacity limitations, and is hence proportional to the attentional demands of both tasks.     

Lactational ethanol exposure: Brain enzymes and [h]spiroperidol binding

Long-Evans lactating rats were fed 27% calories as ethanol in a liquid diet to determine whether alcohol received through the milk would alter normal brain development in the offspring. On days 16, 21 and 30, brains of the female offspring were removed, corpus striatum dissected and assayed for choline acetyltransferase activity, glutamic acid decarboxylase activity and [3H]spiroperidol binding activity. At day 16, there were no differences among the three treatment groups for the enzyme activities assayed. At day 21, glutamic acid decarboxylase activity in the pairfed group was higher than in ET and CT groups. Choline acetyltransferase activity in PF group was higher when compared to ad libitum controls and [3H]spiroperidol binding was not affected. At 30 days of age, animals exposed to ethanol had higher choline acetyltransferase activity and [3H]spiroperidol binding activity when compared to pairfed and ad libitum controls; and higher glutamic acid decarboxylase activity when compared to ad libitum controls. Data from the present study suggest that ethanol exposure during the brain growth spurt has a toxic effect on the late development of dopaminergic, cholinergic and GABAergic systems in the corpus striatum. These results may be related to the clinical symptoms of hyperactivity and problems with motor control in children exposed to alcohol during the third trimester and during lactation.     

Impaired performance on advanced Theory of Mind tasks in children with epilepsy is related to poor communication and increased attention problems

Children with epilepsy (CWE) have social difficulties that can persist into adulthood, and this could be related to problems with understanding others' thoughts, feelings, and intentions. This study assessed children's ability to interpret and reason on mental and emotional states (Theory of Mind) and examined the relationships between task scores and reports of communication and behavior. Performance of 56 CWE (8–16 years of age) with below average IQ (n = 17) or an average IQ (n = 39) was compared with that of 62 healthy controls with an average IQ (6–16 years of age) on cognition, language, and two advanced Theory of Mind (ToM) tasks that required children to attribute mental or emotional states to eye regions and to reason on internal mental states in order to explain behavior. The CWE-below average group were significantly poorer in both ToM tasks compared with controls. The CWE — average group showed a significantly poorer ability to reason on mental states in order to explain behavior, a difference that remained after accounting for lower IQ and language deficits. Poor ToM skills were related to increased communication and attention problems in both CWE groups. There is a risk for atypical social understanding in CWE, even for children with average cognitive function.