Peter Annas

Gender and age differences in the prevalence of specific fears and phobias

Point prevalence of specific fears and phobias was determined in 704 respondents of 1000 randomly selected adults aged 18-70 yr. A phobia for lightning, enclosed spaces, darkness, flying, heights, spiders, snakes, injections, dentists and/or injuries was defined if subjects reported a fear that was out of conscious control, interfered with life and lead to the avoidance of the feared object [American Psychiatric Association, 1994. Diagnostic and statistical manual of mental disorders (4th edn). Washington, DC: American Psychiatric Press.] Fear intensity was assessed using visual analogue scales. A factor analysis generally supported the classification of fears and phobias into: (1) situational phobias (lightning, enclosed spaces, darkness, flying and heights); (2) animal phobias (spiders and snakes); and (3) mutilation phobias (injections, dentists, injuries). Total point prevalence of any specific phobia was 19.9% (26.5% for females and 12.4% for males). In total, 21.2% women and 10.9% men met criterias for any single specific phobia. Multiple phobias was reported by 5.4% of the females and 1.5% of the males. Animal phobia had a prevalence of 12.1% in women and 3.3% in men. Point prevalence of situational phobia was 17.4% in women and 8.5% in men. For mutilation phobia no gender difference was observed, being presented in 3.2% of the women and 2.7% of the men. Women as compared to men gave higher fear ratings for all objects and situations. Inanimate object fears and phobias were more common in older than younger individuals. Animal fears were more intense in younger than in older individuals. Fear of flying increased and fear of injections decreased as a function of age in women but not in men. Thus, specific fears and phobias are heterogeneous with respect to sex and age distribution.

Human fear conditioning is related to dopaminergic and serotonergic biological markers.

Biological markers for acquisition and extinction of fear conditioning were studied in 40 individuals selected for displaying either good or poor acquisition of fear conditioning. as estimated by the skin conductance response. Participants with a short serotonin transporter (5-HTT) promoter allele or low monoamine oxidase activity in platelets (trbc-MAO) displayed better acquisition than those with only long alleles or high trbc-MAO, whereas participants with a long dopamine D4 receptor (D4DR) exon III allele showed delayed extinction compared with those with only short alleles. The findings, that D4DR exon III and 5-HTT promoter genotypes and trbc-MAO activity are related to human fear conditioning, a basic form of associative learning, are consistent with animal studies suggesting a genetic contribution to fear conditioning. The authors suggest that in humans these genetic mechanisms are partly dopaminergic and serotonergic in origin.

Increase of BDNF Serum Concentration in Lithium Treated Patients with Early Alzheimer's Disease

Preclinical and clinical studies gave evidence that lithium could be useful in the treatment of Alzheimers disease (AD). In experimental investigations, lithium induces brain-derived neurotrophic factor (BDNF). Recent studies have found a decrease of BDNF in the serum and brains of AD patients with potentially consecutive lack of neurotrophic support. We assessed the influence of a lithium treatment on BDNF serum concentration in a subset of a greater sample recruited for a randomized, single-blinded, placebo-controlled, parallel-group multicenter 10-week study, investigating the efficacy of lithium treatment in AD patients. In AD patients treated with lithium, a significant increase of BDNF serum levels, and additionally a significant decrease of ADAS-Cog sum scores in comparison to placebo-treated patients, were found. Diminution of cognitive impairment was inversely correlated with lithium serum concentration. Upregulation of BDNF might be part of a neuroprotective effect of lithium in AD patients. The results of the present investigation encourage performing studies with longer treatment phases to observe potential positive long-term effects of lithium in AD patients.

Heritability and Prevalence of Specific Fears and Phobias in Childhood

Fears and phobias are relatively common in childhood. Both environmental and genetic theories have tried to explain the etiology behind these conditions. However, data supporting the different theories are sparse. To investigate the relative importance of genetic and environmental influences on specific phobias and fears, parental reports of animal, situational, and mutilation fears and phobias were completed for 1106 pairs of 8- to 9-year-old Swedish twins. The prevalence of specific phobias was 7.3% for boys and 10.0% for girls. Genetic. shared environmental, and nonshared environmental effects contributed to individual differences in fears and phobias in young children, but the magnitude of the effects differed between sexes. Shared environmental effects contributed to a general susceptibility for fearfulness. Genetic and nonshared environmental effects, on the other hand, contributed both to the general susceptibility and specific fearfulness, even though these effects primarily were fear specific. These results indicate that both heritable factors as well as environmental factors such as trauma, vicarious learning, and/or negative information are important for differences in fearfulness and phobias--at least in children.

Internal consistency and temporal stability of classically conditioned skin conductance responses

The reliability of classically conditioned skin conductance responses was investigated. Temporal stability was determined in 28 subjects studied three weeks apart (study 1), and internal consistency in 223 subjects studied once (study 2). A discriminative classical conditioning paradigm using slides with a duration of 8 s served as conditioned stimuli (CS) for an aversive unconditioned noise stimulus (study 1) or a mild unconditioned electric shock stimulus (UCS) (study 2). Electrodermal responses were recorded during a habituation phase (4 trials), an acquisition phase, where CS+ was paired repeatedly with the UCS, while CS- never was (8 trials), and an extinction phase during which shocks were withheld (8 trials each). First interval responses were measured 1-4 s after CS- onset during all phases of the experiment. During the acquisition and extinction phases, second interval responses were scored 5-9 s after CS- onset while third interval responses were determined 1-4 s after CS- termination. Internal consistency was significant for the first (rxy range 0.96-0.90), second (rxy range 0.84-0.54) and third (rxy range 0.96-0.86) skin conductance interval response. Temporal stability was highest for the first interval response (rxy range 0.72-0.37) and lowest for the second interval response (rxy range 0.51-0.05). It is concluded that the first interval skin conductance response shows adequate internal consistency and temporal stability to assess individual differences in classical conditioning.

Performance on a pattern separation task by Alzheimer’s patients shows possible links between disrupted dentate gyrus activity and apolipoprotein E ∈4 status and cerebrospinal fluid amyloid-β42 levels

IntroductionEmerging evidence suggests that decreased adult hippocampal neurogenesis represents an early critical event in the course of Alzheimer’s disease (AD). In mice, adult neurogenesis is reduced by knock-in alleles for human apolipoprotein E (ApoE) ∈4. Decreased dentate gyrus (DG) neural progenitor cells proliferation has been observed in the triple-transgenic mouse model of AD (3xTg-AD); this reduction being directly associated with the presence of amyloid-β (Aβ) plaques and an increase in the number of Aβ-containing neurons in the hippocampus. Cognitive tasks involving difficult pattern separations have been shown to reflect DG activity and thus potentially neurogenesis in both animals and man. This study involved the administration of a pattern separation paradigm to Alzheimer’s patients to investigate relationships between task performance and both ApoE status and cerebrospinal fluid (CSF) Aβ42 levels.MethodsThe CDR System pattern separation task involves the presentation of pictures that must later be discriminated from closely similar pictures. This paper presents pattern separation data from 66 mild to moderate AD patients, of which 50 were genotyped and 65 in whom CSF Aβ42 was measured.ResultsApoE ∈4 homozygotes were not compromised on the easy pattern separations compared with the other patients, but they were statistically significantly poorer at the difficult separations. In all patients CSF Aβ42 correlated significantly with the ability to make the difficult discriminations, but not easier discriminations. Pattern separation speed correlated negatively with CSF Aβ42, and thus the association was not due to increased impulsivity.ConclusionsThese are, to our knowledge, the first human pattern separation data to suggest a possible genetic link to poor hippocampal neurogenesis in AD, as well as a relationship to Aβ42. Therapies which target neurogenesis may thus be useful in preventing the early stages of AD, notably in ApoE ∈4 homocygotes.

Lithium as a Treatment for Alzheimer’s Disease: A Systematic Review and Meta-Analysis

BACKGROUND This is the first meta-analysis of randomized placebo-controlled trials testing lithium as a treatment for patients with Alzheimers disease (AD) and individuals with mild cognitive impairment (MCI). METHODS The primary outcome measure was efficacy on cognitive performance as measured through the Alzheimers Disease Assessment Scale cognitive subscale or the Mini-Mental State Examination. Other outcome measures were drug discontinuation rate, individual side effects, and biological markers (phosphorylated tau 181, total tau, and amyloid-β42) in cerebrospinal fluid (CSF). RESULTS Three clinical trials including 232 participants that met the studys inclusion criteria were identified. Lithium significantly decreased cognitive decline as compared to placebo (standardized mean difference = -0.41, 95% confidence interval = -0.81 to -0.02, p = 0.04, I2 = 47% , 3 studies, n = 199). There were no significant differences in the rate of attrition, discontinuation due to all causes or adverse events, or CSF biomarkers between treatment groups. CONCLUSIONS The results indicate that lithium treatment may have beneficial effects on cognitive performance in subjects with MCI and AD dementia.

Influence of Lithium Treatment on GDNF Serum and CSF Concentrations in Patients with Early Alzheimers Disease

Preclinical and clinical studies gave evidence that lithium could be useful in the treatment of Alzheimers disease (AD). One possible mechanism of action might be the induction of neurotrophins. Recently, we found a significant increase of brain-derived neurotrophic factor (BDNF) serum levels in AD patients treated with lithium and a significant decrease of ADAS Cog sum scores in comparison to placebo-treated patients. In another previous study we have shown that glial cell line-derived neurotrophic factor (GDNF) levels in CSF of patients with early AD are increased most probably due to an upregulated expression in CNS as an adaptive process of the impaired brain to enhance neurotrophic support at least in early stages of disease. Here we assessed the influence of a lithium treatment on GDNF serum and cerebrospinal fluid (CSF) concentrations in a subset of a greater sample recruited for a randomized, single-blinded, placebo-controlled, parallel-group multicenter 10-week study, investigating the efficacy of lithium treatment in AD patients. We found a significant negative correlation of lithium concentration in serum with GDNF concentration in CSF at the end of treatment (r = -0.585, p = 0.036) and with the difference of GDNF concentration in CSF before and after treatment (r = - 0.755, p = 0.003). However, we could not show a difference in GDNF concentrations between the patients after the treatment with lithium or placebo (serum, mean ± standard deviation: 434.3 ± 117.9 pg/ml versus 543.8 ± 250.0 pg/ml, p = 0.178; CSF, 62.3 ± 37.4 pg/ml versus 72.8 ± 43.9 pg/ml, p = 0.511). The findings of the present investigation indicated that beneficial effects of the lithium treatment might reduce the necessity of enhanced GDNF expression in the CNS in early AD.

The Genetic Covariation between Fear Conditioning and Self-Report Fears

BACKGROUND Fear conditioning is a traditional model for the acquisition of phobias, whereas behavioral therapies use processes underlying extinction to treat phobic and other anxiety disorders. Furthermore, fear conditioning has been proposed as an endophenotype for genetic studies of anxiety disorders. Although prior studies have demonstrated that fear conditioning and self-report fears are heritable, no studies have determined whether they share a common genetic basis. METHODS We obtained fear conditioning data from 173 twin pairs from the Swedish Twin Registry who also provided self-report ratings of 16 common fears. With multivariate structural equation modeling, we analyzed factor-derived scores for the subjective fear ratings together with the electrophysiologic skin conductance responses during habituation, acquisition, and extinction to determine the extent of their genetic covariation. RESULTS Phenotypic correlations between experimental and self-report fear measures were modest and, counter-intuitively, negative (i.e., subjects who reported themselves as more fearful had smaller electrophysiologic responses). Best-fit models estimated a significant (negative) genetic correlation between them, although genetic factors underlying fear conditioning accounted for only 9% of individual differences in self-report fears. CONCLUSIONS Experimentally derived fear conditioning measures share only a small portion of the genetic factors underlying individual differences in subjective fears, cautioning against relying too heavily on the former as an endophenotype for genetic studies of phobic disorders.

Norms for healthy adults aged 18-87 years for the Cognitive Drug Research System: An automated set of tests of attention, information processing and memory for use in clinical trials.

The Cognitive Drug Research (CDR) System is a set of nine computerized tests of attention, information processing, working memory, executive control and episodic memory which was designed for repeated assessments in research projects. The CDR System has been used extensively in clinical trials involving healthy volunteers for over 30 years, and a database of 7751 individuals aged 18–87 years has been accumulated for pre-treatment data from these studies. This database has been analysed, and the relationships between the various scores with factors, including age, gender and years of full-time education, have been identified. These analyses are reported in this paper, along with tables of norms for the various key measures from the core tasks stratified by age and gender. These norms can be used for a variety of purposes, including the determination of eligibility for participation in clinical trials and the everyday relevance of research findings from the system. In addition, these norms provide valuable information on gender differences and the effects of normal ageing on major aspects of human cognitive function.