Unearthing the nonassociative origins of fears and phobias: A rejoinder

In recent years numerous disagreements and controversies have ensued over the place of Pavlovian or associative conditioning in the etiology of specific phobias and other fear-related clinical syndromes. A major source of disagreement emerged from clinical observations suggesting that environmental aversive conditioning events could not be identified for many specific phobias. Part of the controversy can also be traced to disagreements over what constitutes a direct conditioning event and over what exactly is being conditioned in phobic acquisition. More fundamental, however, is confusion over the critical process variables involved in the conditioning etiology of human phobias and fear-related clinical syndromes. We address some of the recent controversies surrounding associative conditioning accounts of phobic onset in light of recent proposals that nonassociative factors account for the etiology of many specific phobias. The viability of the nonassociative position is questioned and alternatives are suggested that emphasize the complex and multifaceted processes involved in the etiology of specific phobias.     

Familial transmission of simple phobias and fears. A preliminary report

Preliminary data from a blind direct interview family study indicate a significantly higher risk for simple phobia among first-degree relatives (n = 49) of simple phobic probands (who had no other anxiety disorder) as compared with first-degree relatives (n = 119) of never mentally ill controls (31% vs 11%, relative risk = 3.3). Female relatives were more likely to be affected than male relatives (48% vs 13%), though this difference did not reach conventional significance in an age-corrected analysis. Significant between-group differences were not found in risks for (1) other anxiety, affective, and substance abuse disorders, and (2) simple irrational fears that did not meet disorder criteria. The results suggest that simple phobia is a highly familial disorder that does not transmit increased risk for other phobic or anxiety disorders. The specificity of increased risk among the relatives of simple phobics is consistent with the distinction between simple phobia, social phobia, and agoraphobia. However, complete delineation of the transmissional relationship between these illnesses requires assessment of the extent to which risk for simple phobia can be transmitted by individuals with other phobic or anxiety disorders. Replication of these preliminary findings in larger clinically and epidemiologically selected samples is needed.     

The genetic epidemiology of phobias in women. The interrelationship of agoraphobia, social phobia, situational phobia, and simple phobia.

In 2163 personally interviewed female twins from a population-based registry, the pattern of age at onset and comorbidity of the simple phobias (animal and situational)--early onset and low rates of comorbidity--differed significantly from that of agoraphobia--later onset and high rates of comorbidity. Consistent with an inherited "phobia proneness" but not a "social learning" model of phobias, the familial aggregation of any phobia, agoraphobia, social phobia, and animal phobia appeared to result from genetic and not from familial-environmental factors, with estimates of heritability of liability ranging from 30% to 40%. The best-fitting multivariate genetic model indicated the existence of genetic and individual-specific environmental etiologic factors common to all four phobia subtypes and others specific for each of the individual subtypes. This model suggested that (1) environmental experiences that predisposed to all phobias were most important for agoraphobia and social phobia and relatively unimportant for the simple phobias, (2) environmental experiences that uniquely predisposed to only one phobia subtype had a major impact on simple phobias, had a modest impact on social phobia, and were unimportant for agoraphobia, and (3) genetic factors that predisposed to all phobias were most important for animal phobia and least important for agoraphobia. Simple phobias appear to arise from the joint effect of a modest genetic vulnerability and phobia-specific traumatic events in childhood, while agoraphobia and, to a somewhat lesser extent, social phobia result from the combined effect of a slightly stronger genetic influence and nonspecific environmental experiences.     

Listening to our clinical partners: informing researchers about children's fears and phobias.

We surveyed a national sample of clinical psychologists to expand on Graziano and De Giovanni's (Behaviour Research and Therapy, 1979, 17, 161-162) findings that 6.8% of clinically referred children present with problems with fears and/or phobias. The survey was also conducted to assess how clinicians could inform researchers about current needs for investigations in this area. Questions involved epidemiological, demographical, and treatment characteristics of cases recently seen by therapists. The percentage of referred cases for fears/phobias in children was determined to be similar over time. In addition, types of fears, length of history of fear, intensity of fear, length of treatment, types of treatments used, and degree of parental involvement were measured and reported. The results were found to suggest a substantial degree of heterogeneity among types of fears and treatment methods for this population, as well as important lines of future research. They also suggest the need for controlled studies to assess the efficacy of a number of widely used treatments that lack an empirical base.     

The orality in phobias

Summary An attempt has been made to focus on the orality in the phobic reaction. The fear of losing control of oral hostility and the fear of oral incorporative guilt are ego-threatening and may be handled by phobic avoidance. Aichmophobia or the dread of sharp objects is presented not as an oedipal or castration anxiety but as fundamentally an oral solution in a decompensating ego.     

The genetic epidemiology of personality disorders

Genetic epidemiologic studies indicate that all ten personality disorders (PDs) classified on the DSM-IV axis II are modestly to moderately heritable. Shared environmental and nonadditive genetic factors are of minor or no importance. No sex differences have been identified. Multivariate studies suggest that the extensive comorbidity between the PDs can be explained by three common genetic and environmental risk factors. The genetic factors do not reflect the DSM-IV cluster structure, but rather: i) broad vulnerability to PD pathology or negative emotionality; ii) high impulsivity/low agreeableness; and iii) introversion. Common genetic and environmental liability factors contribute to comorbidity between pairs or clusters of axis I and axis II disorders. Molecular genetic studies of PDs, mostly candidate gene association studies, indicate that genes linked to neurotransmitter pathways, especially in the serotonergic and dopaminergic systems, are involved. Future studies, using newer methods like genome-wide association, might take advantage of the use of endophenotypes.     

The genetic epidemiology of multiple sclerosis

Multiple sclerosis (MS) is a debilitating immunological and neurodegenerative disorder. Epidemiological studies have provided overwhelming evidence of complex genetic susceptibility to MS. However, with the exception of the human leukocyte antigen (HLA) locus, genetic studies have failed to consistently identify significant linkage or association with genes that modulate MS disease expression. Numerous functional candidate gene studies, linkage genomic screens, and locational candidate gene studies have been performed in an attempt to identify additional loci. However, these methods have demonstrated insufficient power to consistently identify genes or epigenetic factors for MS. More current approaches integrate information from a variety of sources (e.g. consistent linkage data, gene expression profiling, and functional characterization studies) and utilize high throughput methods (e.g. genotyping high density markers, utilizing pooling schemes and performing new statistical analyses) in an attempt to overcome power issues. The following article presents a review of MS genetics research and a brief overview of methods that are currently being developed and utilized for fine localization of MS loci, such as the method employed in the Genetic Analysis of Multiple sclerosis in EuropeanS (GAMES) study that is presented elsewhere in this journal. It is the hope of researchers that these methods will lead to the identification of susceptibility genes for MS that aid in elucidating pathogenic mechanisms and potential therapeutic strategies for this debilitating disease.     

The genetic epidemiology of bulimia nervosa.

OBJECTIVE: The authors seek to clarify, from both an epidemiologic and genetic perspective, the major risk factors for bulimia nervosa and to understand the relationship between narrowly defined bulimia and bulimia-like syndromes. METHOD: Personal structured psychiatric interviews were conducted with 2,163 female twins from a population-based register. Psychiatric disorders were assessed using DSM-III-R criteria. RESULTS: Lifetime prevalence and risk for narrowly defined bulimia were 2.8% and 4.2%, respectively. Including bulimia-like syndromes increased these estimates to 5.7% and 8.0%, respectively. Risk factors for bulimia included 1) birth after 1960, 2) low paternal care, 3) a history of wide weight fluctuation, dieting, or frequent exercise, 4) a slim ideal body image, 5) low self-esteem, 6) an external locus of control, and 7) high levels of neuroticism. Significant comorbidity was found between bulimia and anorexia nervosa, alcoholism, panic disorder, generalized anxiety disorder, phobia, and major depression. Proband-wise concordance for narrowly defined bulimia was 22.9% in monozygotic and 8.7% in dizygotic twins. The best-fitting model indicated that familial aggregation was due solely to genetic factors with a heritability of liability of 55%. A multiple threshold model indicated that narrowly defined bulimia nervosa and bulimia-like syndromes represented different levels of severity on the same continuum of liability. CONCLUSIONS: The liability to fully syndromal bulimia nervosa, which affects around one in 25 women at some point in their lives, is substantially influenced by both epidemiologic and genetic risk factors. The same factors that influence the risk for narrowly defined bulimia also influence the risk for less severe bulimia-like syndromes.     

Agoraphobia between panic and phobias: clinical epidemiology from the Sesto Fiorentino Study

In the last few decades, there has been a long debate on the existence of agoraphobia (AG) without a history of panic attacks (PAs). In the present study, the problem of the relationships between AG and PAs is addressed trough a reevaluation of the cases who had been diagnosed with AG in the community survey of Sesto Fiorentino. Forty-one of the 75 subjects who met the criterion of AG in the Sesto Fiorentino Study were reinterviewed by experienced clinical psychiatrists. The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and the Composite International Diagnostic Interview were used to make the diagnoses. The Mobility Inventory for Agoraphobia (MIA) and a specific adjunctive question, “why do/did you avoid?,” were used to compare AG subjects with or without PD. Of the 41 subjects with a lifetime history of AG, 12 cases had original diagnosis of AG without PAs and the remaining 29 had PD with AG. After the reassessment, in 10 cases, the criteria for the diagnosis of AG without PAs were confirmed, totaling a lifetime prevalence of 0.4% (confidence interval, 0.2-0.8). Agoraphobia subjects with and without PAs were comparable as regard to sex, age, age of onset, duration of illness, family history for anxiety or mood disorders, MIA scores, number, and type of situations avoided. Thus, AG seems to exist also in absence of a history of PAs, and the one-way relationship between the occurrence of PAs and a following development of AG, postulated by DSM-IV, should be reconsidered for the future classifications.     

The onset of driving phobias

Thirty driving phobics who called the Psychiatry Outpatient Phobia Clinic (25 females and five males) were given a 20-min semi-standardized telephone interview during which they were asked about the circumstances of the onset of their driving fears. Twelve (40%) reported that their fears were precipitated by a panic attack on the freeway; six (20%) by a collision; and three (10%) by other frightening experiences in automobiles. Four (13.3%) related the onset to family stress or upheaval. Other modes of onset also occurred. The implications of these findings are discussed in terms of existing theories of fear acquisition and treatment approaches.     

The genetic epidemiology of schizophrenia and of schizophrenia spectrum disorders

It has been known for a long time that schizophrenia and several related psychopathological traits aggregate in families on a common genetic basis. Improved methodology of recent family, twin and adoption studies has led to a better understanding of which psychopathologically defined syndromes and personality traits are part of a schizophrenia spectrum, and to which degree individual spectrum conditions share the same genetic background with schizophrenia. The spectrum concept has been extended to include neuropsychologically, neurophysiologically and neuroradiologically measurable familial traits as subclinical endophenotypes of schizophrenia that may be more fundamental to the development of the disease than overt psychopathology. This knowledge has been useful in designing molecular genetic linkage and association studies the aim at directly identifying individual risk genes. Replicable linkage findings have emerged from genome scans that imply at least seven chromosomal regions to harbour schizophrenia susceptibility genes. They strengthen the conviction that schizophrenia is indeed a genetically complex disorder, based on a larger number of susceptibility genes with risk-increasing alleles that are common in the population and exert a limited effect on the individual level. Although demanding increased investments into sample collection, genotyping and computational technology, identification of these genetic variants will be possible and worthwhile since they may have a large effect in terms of population attributable risk. Received: 3 March 2000 / Accepted: 24 March 2000     

Specific fears and phobias in the general population: Results from the Netherlands Mental Health Survey and Incidence Study (NEMESIS)

OBJECTIVE: To examine the prevalence rate, impairment, comorbidity, course of illness and determinants of eight specific phobia variants: animals (animal subtype); heights, water, storms (natural environment subtype); flying, enclosed spaces, being alone (situational subtype); and blood/injury (blood/injury subtype). METHOD: Data were obtained from the Netherlands Mental Health Survey and Incidence Study, a prospective study in the Dutch general population aged 18-65 (N = 7,076). RESULTS: The most prevalent condition was specific phobia with a fear of heights (4.9%). On all parameters except duration, specific phobia with a fear of being alone emerged as the most severe condition. Phobias with fear of enclosed spaces and phobias with fear of blood showed a slightly greater likelihood of impairment, comorbidity and personality problems than phobias with fear of animals, heights, water or storms. CONCLUSION: The situational and blood/injury phobia subtypes appear to be a more significant index for impairments and for comorbid psychiatric disorders than the animal and natural environment phobia subtypes.     

The genetic epidemiology of schizophrenia and the design of linkage studies

Summary There are three aspects of schizophrenia that are challenges to the design of linkage studies. First, analysis of twin and family data have consistently failed to identify a single major gene effect. Second, ascertainment of multiplex families does not guarantee the sampling of families in whom a major gene is segregating even if such a gene exists. Third, environmental influences appear to play an essential role in the etiology of at least some schizophrenia. The implications of these features for linkage strategies in schizophrenia are discussed.A previous version of this paper was published in Schizophrenia Bulletin (1989, 15:453–464) and reprinted in V. Bulyzhenkov, Y. Chirsten, L. Prilipko (eds) (1990) Genetic approaches in the prevention of mental disorders, Berlin: Springer-Verlag, pp 24–38     

Genetic aspects and genetic epidemiology of parasomnias

Parasomnias are undesirable phenomena associated with sleep. Many of them run in families, and genetic factors have been long suggested to be involved in their occurrence. This article reviews the present knowledge of the genetics of the major classical behavioral parasomnias as well as present results from genetic epidemiological studies. The level and type of evidence for genetic effects varies much from parasomnia to parasomnia. The genetic factors are best established in enuresis, with several linkages to chromosomal loci, but their functions are not so far known. Environmental causes and gene-environment interactions are most probably also of great importance in the origin of complex traits or disorders such as parasomnias.     

The use of genetic epidemiology to guide classification in child and adult psychopathology

The goal of this paper is to illustrate the application of the tools of genetic epidemiology, particularly the family study method, to inform the classification of psychiatric disorders in adults and children. The first section describes family studies of adults designed to investigate the causes of comorbidity of anxiety and depression. The analysis of familial traits provides stronger evidence for the validity of certain sub-types of anxiety and mood disorders that co-occur within the same individual and within families. The second section presents an example of the use of the family study method to examine the validity of the autism spectrum disorders (ASD). A review of these studies suggests that the most consistently familial traits in ASD are language and communication skills, insistence on sameness and non-verbal IQ. These are also the traits most commonly associated with the differentiation of autism from Asperger disorder and PDDNOS using both cross-sectional and longitudinal studies. From these data, a new classification system of the ASDs is proposed based on these familial traits.     

The use of genetic epidemiology to guide classification in child and adult psychopathology

The goal of this paper is to illustrate the application of the tools of genetic epidemiology, particularly the family study method, to inform the classification of psychiatric disorders in adults and children. The first section describes family studies of adults designed to investigate the causes of comorbidity of anxiety and depression. The analysis of familial traits provides stronger evidence for the validity of certain sub-types of anxiety and mood disorders that co-occur within the same individual and within families. The second section presents an example of the use of the family study method to examine the validity of the autism spectrum disorders (ASD). A review of these studies suggests that the most consistently familial traits in ASD are language and communication skills, insistence on sameness and non-verbal IQ. These are also the traits most commonly associated with the differentiation of autism from Asperger disorder and PDDNOS using both cross-sectional and longitudinal studies. From these data, a new classification system of the ASDs is proposed based on these familial traits.     

Socially related fears following exposure to trauma: environmental and genetic influences

Few studies have examined why socially related fears and posttraumatic stress commonly, but not invariably, co-occur. It may be that only traumata of human agency (e.g., sexual assault), for which there is an interpersonal component, give rise to co-occurring socially related fears. These symptoms might also co-occur because of shared genetic factors. We investigated these issues using a sample of 882 monozygotic and dizygotic twins. No significant differences in socially related fear (i.e., fear of negative evaluation, fear of socially observable arousal symptoms) were found between participants reporting assaultive or nonassaultive trauma. However, significant differences in socially related fear were found when participants were grouped into probable PTSD and no PTSD groups. Participants with probable PTSD exhibited greater socially related fear (i.e., fear of negative evaluation) than those without PTSD. Using biometric structural equation modeling, trauma exposure was best explained by shared and nonshared environmental influences. The fear of socially observable arousal symptoms was influenced by genetic and nonshared environmental influences. Implications and directions for future research are discussed.     

The genetic epidemiology of psychiatric disorders: a current perspective

Psychiatric genetic epidemiology has, as a field, undergone considerable change in the last two decades. My goal here is to provide a brief, selective and inevitably personal overview of where the field has come from, where it is now and where it might be going. Methodologic issues will be emphasized, particularly those of an epidemiologic nature. I will organize this review around three of the major methods used in psychiatric genetics: family studies, twin studies and linkage studies.