The Neuropsychological Implications of Prenatal Alcohol Exposure

Introduction

Alcohol is a neurobehavioral teratogen in that it causes brain damage and modifies behavior (Riley and Vorhees, 1986). The teratogenic effects of alcohol on the developing brain can occur at lower doses and frequency of exposure than required for the physical manifestations of FASD such as the characteristic facial features or growth restriction. Because the brain is constantly developing throughout gestation, the effects of prenatal alcohol exposure on the developing brain can occur at any point. Therefore, exposure at different times and with different doses during gestation may explain why FASD presents as a spectrum of central nervous system dysfunction. In addition, individual differences in the mother and child modify the effect of prenatal exposure in the individual, and not every child exposed is affected (Streissguth, 1997). Overall, the behavioral and cognitive difficulties seen in FASD are modulated by other biologic and environmental factors, making a diagnosis of FASD only one of many contributing factors to a particular individual’s profile (Stratton et al, 1996). Prenatal alcohol exposure can result in primary deficits in cognition and behavior. In addition, these primary disabilities can cause secondary disabilities and psychiatric co-morbidities.

Primary Disabilities

The primary disabilities seen in FASD arise from direct brain damage. The most consistent finding from prenatal alcohol exposure is reduction in brain weight and this can result in microcephaly (Jacobson and Jacobson, 2003). Prenatal alcohol exposure is known to disrupt many areas of brain development, including the cerebellum, hippocampus, basal ganglia, and the corpus callosum (Sowell et al, 2001; Mattson, Schoenfeld, and Riley, 1999). Other pathologic changes to the central nervous system include enlarged ventricles, abnormal neural/glial migration, and changes in the microvasculature in regions of the brain such as the cerebellum and hippocampus (Miller, 1992).

Research to date has not identified a single prototypical cognitive profile, and it is unlikely that one specific behavioral or cognitive phenotype for FASD will emerge. More likely, there will be identifiable patterns related to differential alcohol exposure (timing, amount, and frequency), combined with other genetic and environmental factors. These patterns may be reflective of general patterns of atypical prenatal brain development due to a combination of factors, and may not be specific to alcohol as a teratogen. However, some of the more commonly identified problem areas in FASD include attention, learning and memory, abstract problem solving and strategy generation. While individuals with FASD will often be within normal limits on measures of IQ, they often have other significant neurocognitive deficits. Many areas of cognitive functioning are only peripherally assessed through an IQ measure, such as attention and concentration. In addition, IQ testing does not assess other domains, such as higher order executive functions. These deficits will have a profound effect on the ability of a person with FASD to function, and without appropriate supports and interventions this can lead to secondary impairments.

In regard to general intellectual functioning, early work in this field led to the misperception that individuals with FASD fell within the mentally retarded range (Darby, Streissguth, and Smith, 1981). More comprehensive studies indicate that approximately 25% of persons with FAS and less than 10% of persons with FAE would qualify for funding if a diagnosis of mental retardation was required (Streissguth et al, 1996). This later study, based on a large cohort of individuals with FASD, reported full scale IQ’s in the FAS group that ranged from 20 to 120, with a mean IQ score of 79. In the FAE group full scale IQ scores ranged from 49 to 142, with a mean IQ score of 90. It is also not unexpected to see an apparent decrease in IQ performance on sequential assessment in an individual with FASD. However, this is not related to an underlying deteriorative process. Rather, these individuals often fail to make age-appropriate gains in intellectual functioning based on normative performance, even though they continue to show improvements in their raw scores. Part of this failure is related to other deficits such as impaired learning and memory, as well as secondary disabilities that interfere with progress in mainstream academic programming.

Memory impairments are another common deficit in individuals with FASD. More specifically, they are prone to intrusion errors and confabulation, difficulties with strategic manipulation of information to improve recall, and difficulties with initial encoding of information. The nature of memory impairments related to encoding difficulties is due to hippocampus damage, while impaired frontal lobe functioning can cause free recall and intrusion/confabulation difficulties. However, short-term immediate verbal recall is often well developed in individuals with FASD, which can lead to a false impression of “good memory” functioning. Individuals with FASD will also have problems with working memory. While many aspects of explicit memory functioning or conscious memory recall have been found to be impaired, implicit memory functioning or procedural or unconscious recall typically functions within normal limits (Mattson & Riley, 1999), which could have significant implications for remediation and vocational training.

Basic language abilities are often found to be a relative strength in FASD. It is often recognized that they are very adept at “parroting back” verbal information that they have heard. However, while they tend to be loquacious, their verbal communication is lacking in complex meaningful content and their actual comprehension of complex material often is significantly compromised. Mixed expressive-receptive language disabilities are often diagnosed in these children. Severe language delays are seen more commonly in children diagnosed with the full manifestations of FAS (Adnams et al, 2001).

Visual-motor integration and visual-perceptual deficits are also commonly reported in FASD. Some potential problems with deficits in this area can include reading disorders, impaired appreciation of spatial orientation, and these can impede the ability to detect and understand nonverbal communication that is critical to successful social interaction.

FASD individuals are often identified with learning disabilities. Specifically, mathematics skills are often impaired, especially relative to their single word reading and spelling abilities. This often manifests as difficulties with money management and telling time. Significant reading comprehension and written expression, and learning impairments are also common, and these typically become more evident as the child progresses through school.

Poor response inhibition, impulsiveness, and perseverative behavior also present a problem for an individual with FASD, often giving them the appearance of having Attention Deficit Hyperactivity Disorder. In a review of the literature on the link between ADHD and FASD, it has been asserted that in children with FASD, ADHD is more likely to be of earlier-onset, inattention subtype, and to have comorbid developmental, psychiatric, and medical conditions (O’Malley and Nanson, 2002). Other researchers have found that FASD children do not show deficits in sustained attention, the ability to remain alert over time, but have deficits in focused attention, the ability to maintain attention in the presence of distraction (Coles et al, 1997; Coles, 2001). Hyperactivity may also be attributable in FASD to social and environmental factors that frequently accompany the diagnosis including attachment disorder, post traumatic stress disorder and anxiety disorders (Jacobson and Jacobson, 2003). ADHD in children with FASD is also more often poorly responsive to standard medical intervention, including psychostimulants (O’Malley et al, 2000).

Executive functioning, including the ability to plan, cognitive flexibility, selective inhibition, and concept formation, has consistently been reported to be impaired in FASD. These difficulties can be apparent in measures designed to be more sensitive to dorsolateral frontal lobe functioning such as the Wisconsin Card Sorting Test, as well as on measures sensitive to orbital medial frontal lobe functioning such as response inhibition testing. These impairments will often lead to marked adaptive deficits. For example, their ability to problem solve and make appropriate choices in emotionally-weighted or social situations is significantly compromised. This is further confounded by their compromised ability to generate effective alternate strategies to solve a problem, even if they recognize that their first attempt was not successful.

Individuals with FASD can also be compromised in their ability to take the perspective of another person. Self-reflection and insight into their actions is typically very limited. Therefore, they will often fail to demonstrate effective reciprocal social behavior, which serves to alienate them from others.

Adaptive skills are also consistently reported to be deficient in individuals with FASD (Thomas et al, 1998). Particular areas of adaptive impairment include social skills, emotional maturity, money and time concepts, and comprehension. On the other hand, physical maturity, basic reading ability, and basic expressive language abilities tend to be normally developed or only mildly impaired. As a result, these individuals may appear physically mature, are able to meet basic literacy demands, and are able to use relatively sophisticated language. This combination of relative strengths will give them the appearance of functioning at a level consistent with their chronological age. However, their other deficits often impede their ability to function independently. This mismatch between the demands and expectations placed upon them as compared to their actual underlying ability likely contributes to the development of secondary disabilities common in FASD.

Neuropsychological Assessment of Primary Disabilities

A comprehensive neuropsychological assessment is important to assess all areas of neurocognitive and adaptive functioning, and should explore patterns of strengths and weaknesses. This should include an assessment of sensory perceptual functioning, gross and fine motor skills, visual-motor integrative abilities, visual-spatial and visual-perceptual skills, attention and processing speed, expressive and receptive language, auditory and visual learning and memory, executive functioning, and both IQ and academic testing. This information should be combined with adaptive and behavioural data, using tools such as the Behaviour Assessment System for Children, Conner’s, and the Adaptive Behaviour Assessment System. Patterns of weaknesses can be used to help determine the presence of chronic organic brain dysfunction, which is a critical component of arriving at a FASD diagnosis. Identified strengths can provide valuable information to help the treatment team develop individualised treatment programs.

Comprehensive neuropsychological assessment may not be available in all cases due to limited resources or a lack of available professionals. Another means of undertaking a comprehensive neuropsychological assessment is through the use of a team of interdisciplinary health care providers, including a speech-language pathologist, occupational therapist, and psychologist. A full psychological assessment will be able to provide useful information for treatment planning and helping other professionals better understand the psychological functioning of the person identified with FASD. Unfortunately, the diagnostic risk of false negatives when relying solely on a general psychological assessment or basic cognitive screening tools is high due to the probability of their IQ and basic rote verbal skills being within normal limits, while many other critical areas of cognitive functioning are significantly impaired. Therefore, when the clinical picture of disability is not fully captured by a basic psychology assessment, consideration should be made to undertake a comprehensive neuropsychological assessment. It is important to note that the cognitive and behavioural profile of children with FASD can change over time. Therefore, repeated neuropsychological assessment may be needed at different times during the life of an individual with FASD to refine their FASD brain-related diagnosis, and to accurately capture their evolving strengths and weaknesses, and to plan appropriate interventions.

Diagnostic Models for Brain Dysfunction

In the past, diagnostic approaches and guidelines were based on a gestalt approach (Sokol and Clarren, 1989; Rosett, 1980; Clarren and Smith, 1978). At present there are two different models for diagnosing fetal alcohol spectrum disorders: the Institute of Medicine (IOM) model (Stratton et al, 1996), and the FASDiagnostic and Prevention Network (DPN) model (Astley and Clarren, 1999). Both of these diagnostic models have specific approaches to understanding brain dysfunction in individuals with FASD, and were developed to make FASD diagnoses more objective, explicit, reliable and valid.

The Institutes of Medicine Model

The IOM model was the first attempt to define a consensus approach to the diagnosis of FASD (Stratton et al, 1996). The IOM committee delineated five diagnostic categories for FASD. These include FAS with a confirmed maternal alcohol exposure, FAS without confirmed maternal alcohol exposure, partial FAS with confirmed maternal alcohol exposure, alcohol–related neurodevelopmental disorder (ARND), and alcohol-related birth defects (ARND) (Stratton et al, 1996). One of the key questions raised by the IOM committee was “can behavioral or cognitive features be used to define the disorder?” The IOM diagnostic criteria for FASD does include evidence for central nervous system or neurodevelopmental abnormalities as one component of the diagnostic framework. They state: “No single expression of structural or functional brain damage is universal or pathognomonic when patients with the FAS face and a clear history for substantial alcohol exposure are reviewed. Evidence of abnormality in this field may be structural, neurologic, or functional (Stratton et al, 1996).” For FAS, this is stipulated as at least one of the following: decreased cranial size at birth, structural brain abnormalities (microcephaly, partial or complete agenesis of the corpus callosum, cerebellar hypoplasia), or neurological hard or soft signs such as impaired fine motor skills, neurosensory hearing loss, poor tandem gait, or poor eye-hand coordination (Stratton et al, 1996). The diagnosis of partial FAS or ARND requires evidence of neurodevelopmental abnormalities as described above, but these diagnoses can also be made based on the finding of evidence for a complex pattern of behavioral or cognitive abnormalities not consistent with developmental stage, and that cannot be explained by familial background or environment. This “complex pattern of behavioral or cognitive abnormalities” is further specified to include learning difficulties, deficits in school performance, poor impulse control, problems in social perception, deficits in higher level receptive and expressive language, poor capacity for abstraction or metacognition, specific deficits in mathematical skills, or problems in memory, attention or judgment (Stratton et al, 1996).

Clearly, the IOM recognized that their work in this area was incomplete as a key recommendation for further research was the “investigation of the differences in expression and specificity of behavioral and cognitive deficits in FAS and ARND (Stratton et al, 1996). They state that “a variety of behavioral and cognitive features have been proposed as indicators of brain dysfunction in FAS…at present, however, no consensus has been achieved as to which features are most appropriate for the diagnosis of FAS, or indeed whether any are appropriate (Stratton et al, 1996).” The IOM also recognized that the behavioral and cognitive effects of prenatal alcohol exposure fall on a continuum that ranges from normality to impaired, that they change with time, that severity of presentation is not necessarily reflective of type of FASD diagnosis, and that FASD can occur in association with other developmental and psychiatric conditions (Stratton et al, 1996). They also acknowledged that the behavioral and cognitive deficits seen in individuals with FASD are also influenced by other factors such as genetic contributions, educational experience, impoverished postnatal environment, and other social and cultural influences (Stratton et al, 1996).

The FAS Diagnostic and Prevention Network Model

The DPN model was developed to address previous limitations in FASD diagnosis via a quantitative approach. Aims of this model are to provide a specific, accurate and precise diagnosis, to provide objective quantitative scales to measure the magnitude of key diagnostic features, and to separate outcome and exposure (Astley and Clarren, 1999; Astley and Clarren, 2000).

The DPN model provides case-definitions for brain damage or dysfunction along a continuum of probability using a Likert scale from 1 (unlikely) to 4 (definite). The 4-point brain dysfunction scale allows patients with clear evidence of brain damage to be differentiated from patients without evidence of brain damage. The higher the number the more certain the patient’s cognitive and behavioral problems stem from brain damage. But a higher score does not necessarily mean a more severe expression of functional disability. A brain ranking of 4 (definite brain damage) and 3 (probable brain damage) are defined as “static encephalopathy.” Static encephalopathy means non-progressive brain dysfunction, but the term does not define or suggest any specific pattern of structural abnormality of cognitive/behavioral dysfunction. (Astley and Clarren, 1999). A Likert rank of 4, or definite organic brain damage, is based on evidence for structural or neurological brain damage, including microcephaly, structural abnormalities on brain imaging likely of prenatal origin, evidence of persistent neurologic findings likely to be of prenatal origin (such as seizure disorder, or cerebral palsy), or a full-scale intelligence quotient (FSIQ) less than or equal to 60 (which was felt to fall clearly below the normal distribution). A Likert rank of 3, or probable organic brain damage, is supported by psychometric test outcomes that document abnormal brain function in three or more areas with test scores that are less than 2 standard deviations below the mean. Although this criterion is not based on scientific data, the authors state that using the cut off of three or more deficits is more reflective of brain damage than one or two areas of deficit, and that this assertion is supported by face validity in their study population. A brain ranking of 2 (possible brain damage) is defined as “neurodevelopmental disorder.” The term neurobehavioral disorder is used when the patient presents with cognitive/behavioral dysfunction, but structural, neurologic and psychometric measures do not unequivocally support the presence of structural brain abnormalities (Astley and Clarren, 1999). A Likert score of 2 is given either to those who are too young to receive psychometric testing, or to those individuals for which there is a strong possibility for brain damage, based on psychometric testing deficits. A brain ranking of 1 (unlikely brain damage) does not receive an FASD brain-related diagnostic label, and is given when there are no identified structural, neurological or cognitive/behavioral problems.

One strength of the DPN model is that it does not establish a causal link between behavioral and cognitive deficits and prenatal alcohol exposure, but rather seeks to establish what an individual’s disabilities/abilities are, and then suggests what etiologic factors are at play. The DPN model recognizes the complexity of development and behavior, and that alcohol related brain damage is only one piece of a dynamic process that can contribute to the complex primary and secondary disabilities seen in FASD.

Secondary Disabilities

Secondary disabilities are the behavioral, cognitive, and psychiatric results of living with brain damage. In individuals with FASD, these include mental health problems, disrupted school experience, trouble with the law, confinement, inappropriate sexual behavior, and problems with dependent living and employment in adults (Streissguth et al, 1996). It is recognized that these problems also include an increased risk of addictive behaviors such as alcohol abuse, thereby potentially continuing the cycle of FASD into the next generation (Baer et al, 2003).

Although mental health problems are the most commonly reported secondary problem across all age groups in FASD, and are seen in up to 90 percent of subjects, studies to date have focused primarily on neurocognitive deficits (Streissguth, 1996; Streissguth and O’Malley, 2000). For many of the problem areas, higher IQ increased the probability of having problems, with the exceptions of dependent living and problems with employment. It was also quite striking that the probability of experiencing secondary disabilities was higher if a FASD diagnosis was made after age six. Overall, the strongest protective factors were a diagnosis before 6-years of age and living in a stable nurturing home (Streissguth, 1997). European long-term follow-up studies have had similar findings, including a high rate of mental health disorders in adulthood and a greater need for social and employment support due to deficits in adaptive functioning (Lemoine and Lemoine, 1992; Spohr, 1996; Steinhausen, 1996). In a population-based study in Seattle, researchers found that prenatal alcohol exposure was the major explanatory variable related to antisocial behavior as well as classroom behavior and learning problems in 14-year-olds. This same study also reported a link between prenatal alcohol exposure and adolescent drug and alcohol use (Olson et al, 1997). Psychiatric illness and DSM-IV diagnoses have also been studied in a sample of children between the ages of 5 and 13 years with heavy prenatal alcohol exposure. Children with IQ’s of 70 and above were assessed and approximately 87 % of the sample met criteria for a psychiatric disorder. The majority (61%) were diagnosed with a mood disorder. Criteria for bipolar disorder were met in 35%, and 26% met criteria for a major depressive disorder or an adjustment disorder with depressed mood. This same study also found that children with partial FAS or no physical stigmata of FAS were just as likely to have significant mental health problems as those with obvious physical characteristics of FAS (O’Connor et al, 2002). Studies in adults with FASD have reported similar findings suggesting that these problems persist in adulthood. In a recent study of adults exposed to alcohol prenatally, 44% were diagnosed with a major depressive disorder, 40% had psychotic disorders, and 20% had bipolar disorder (Famy et al, 1998). One possible explanation for the increased risk of mood disorders comes from recent MRI studies of children prenatally exposed to alcohol compared to adults with depressive disorders. In both groups, there is underdevelopment of the structures controlling mood in the fronto-cortical network, the basal ganglia (in particular the caudate nuclei) and the cerebellum (O’Connor et al, 2002).

Conclusion

Psychiatrists, pediatricians and neuropsychologists must collaborate closely to sort out the complexities of brain and behavior in individuals diagnosed with FASD. Ultimately, it must be recognized that the degree of impairment, including an accurate physical diagnosis, comprehensive testing of the primary disabilities, and close surveillance for secondary disabilities for each person with FASD must be fully explored. A common misperception is that the person with the full manifestations of FAS will be more impaired in all areas as compared to the person diagnosed with another FASD diagnosis. To the contrary, persons with FAS exhibit fewer secondary problems than other FASD, likely due to the fact that they have the physical stigmata of FAS, and hence their impairment is recognized and interventions provided at an earlier age. Without a comprehensive neuropsychological assessment, as this article has outlined, there is a risk of underestimating the degree of impairment in individuals with FASD, and thereby placing inappropriate demands and expectations on them.

It will be necessary in the field of psychiatry to include the FASD diagnosis in the Diagnostic and Statistical Manual of Psychiatric Disorders, so that the unique neurobehavioral and cognitive features of this condition can be accurately identified and diagnosed. Understanding the underlying brain-based aspects of this disorder should assist in improved medical, pharmacological and societal management of individuals affected by this common and ultimately preventable condition.