William R. Clark

Fearwhich in humans ranges from generalized anxiety to specific phobiasis an important biological adaptation and a common behavior in all mammals. Fear is an emotion, an unspoken memory, stored in special parts of the brain. It provokes individuals to react rapidly, almost instinctively, in the face of perceived danger. Fear can be present in greater or lesser degrees in different individuals. When a tendency to fear is present in excess, its consequences are not always helpful.

As many as one fourth of all Americans will suffer from potentially debilitating anxiety, panic disorders, animal phobias and post-traumatic stress reactions at least once in their lives. These disorders cause not only mental anguish but a variety of real physical symptoms, including localized pain. As with other forms of behavior, we would like to know to what extent fear is learned from environmental experience and to what extent it is influenced by our genetic makeup.

Image: BROOKHAVEN NATIONAL LABORATORY GABA MOLECULE. Mice lacking functional nerve cell receptors for this neurotransmitter, gamma-amino butyric acid, are more fearful than mice having the receptor.

The study of fear in animals such as mice has shown that fear can be selectively bred into succeeding generations, suggesting a strong genetic component. Randomly selected mice subjected to an "open-field test"a brightly lit, open box with no hiding placesexhibit a range of different responses. Some mice cower motionless near one wall, defecating and urinating repeatedly, whereas others roam about, sniffing and exploring without concern. Most mice are somewhere between these two extremes. If fearful mice are bred with one another repeatedly over a dozen or so generations, it is possible to develop lines of mice in which all members are highly anxious and fearful in a variety of different tests. But they do not learn this from one another or from their mothers. A newborn mouse from a fearful line, reared by a fearless mother together with fearless siblings, will still be fearful as an adult.

Specific genes associated with such behavior are currently being identified in laboratory mice. Not surprisingly, many of the genes associated with fear or the lack of it encode neurotransmitters or their receptors. These are the molecules within the brain responsible for chemical communication between nerve cells; they ultimately underlie all behavior. Mice lacking functional nerve cell receptors for the neurotransmitter GABA (gamma-amino butyric acid) are more fearful than mice with the receptor.

GABA is used by higher regions of the brain to tone down some of the lower brain's initial impulses and may function to decrease overly fearful responses to environmental stimuli. Similarly, mice lacking a receptor in the brain for glucocorticoid stress hormones are much less anxious than control mice. An unexpected category of genes associated with fearfulness in mice includes some of the genes involved in the operation of biological clocks. How these genes relate to fear is unclear at present, but unraveling their role may shed new light on the origins of fear within the brains of people as well as mice.

There is considerable evidence in humans, derived largely from studies of adopted children, and identical and fraternal twins reared together or apart, that a tendency toward anxiety and fear is a heritable trait. The specific form that fear takesphobias with specific associations, such as snakes, fear of pain, or of heights or closed spacesis almost entirely associated with individual environmental experiences. But the tendency to develop fearful or anxious responses to the environment in general has a clear genetic component.

As with mice, it appears that a major portion of the genetic contribution to human fear and anxiety involves neurotransmitters and their receptors, and again GABA and its receptors play a key role. But perhaps the most important neurotransmitter mediating anxiety in humans is serotonin. Variability in the receptors responsible for clearing serotonin from the synaptic space between two communicating neurons correlates quite well with variation in anxiety among different individuals. Anxiety is closely connected with depression in humans, and drugs that modulate serotonin levels in neuronal synapses also affect both depression and anxiety. Serious depression also has a marked genetic component.

Fear and anxiety are influenced by many genes; there is no such thing as a simple "fear" gene that is inherited from one generation to the next. The genes controlling neurotransmitters and their receptors are all present in several different forms in the general population. The particular combinations of these different forms that we receive from our parents will predispose us to respond with greater or lesser degrees of anxiety to events in our environment. But the degree to which our lives are affected by this inherited predisposition will depend to a very large extent on our individual histories--the number, strength, type and duration of events that elicit such reactions in the first place.