Chapter 4: Generalized Anxiety Disorder (GAD)

Karen Rowa

Heather K. Hood

Martin M. Antony

Diagnosis: Central Features

Excessive worry occurring about a number of different topics

Symptoms of physiological or psychological hyperarousal

DSM-5 Diagnostic Criteria for Generalized Anxiety Disorder (GAD)

Excessive anxiety and worry More days than not for at least 6 months; multiple topics

Difficult to control

Anxiety and worry are associated with ≥ 3 of following:Restlessness or feeling keyed up or on edgeBeing easily fatiguedDifficulty concentrating or mind going blankIrritabilityMuscle tensionSleep disturbance

Diagnosis: Comborbidity

Worry is a common feature of mood disorders~80% of people with GAD also had a comorbid mood

disorderGAD cannot be diagnosed if the worry occurs exclusively

during a mood disorder, PTSD, a psychotic disorder, or PDD

GAD is highly comorbid with: Panic disorder with or without agoraphobia (41%), social

phobia (42%)

Diagnosis: Assessment

Comprehensive assessment of GAD should cover:Beliefs about worry, intolerance of uncertainty, anxiety,

symptoms of hyperarousal, comorbid conditions, goals, areas of behavioral inactivation, and emotional avoidance

Self-report measures of GAD can help assess for presence of diagnostic criteria, severity of worry, and content of worry topics

Symptoms: Worry

GAD worries are indistinguishable in content from “normal” worries

GAD worries differ from normal worries in that:Increased frequency and intensityPerceived inability to control the worry

Distinguishable from cognitions seen in social anxiety disorder and panic disorderMore future-oriented

Symptoms: Avoidance and Checking

Many individuals with GAD engage in behaviors intended to avoid or reduce distress or anxiety

Individuals with GAD endorse similar degrees of checking behavior compared to individuals with OCDChecking in GAD is predominantly interpersonal (e.g.,

seeking reassurance from others)

Symptoms: Functioning

Some individuals with GAD report severe disability across domainsParticularly romantic relationships

Significantly lower overall quality of life and life satisfaction in wider range of areasSelf-esteem, work, health, and social relationships

Prognosis

Chronic and relapsing with some fluctuation in courseProbability of full remission at some point over 5 years is ~38%Probability of partial remission is ~47%

Predictors of a negative clinical course Comorbid Axis I disorders Personality disordersDecreased life satisfactionDifficult family relationships

GAD onset is equally likely to be before or after a major depressive episode, indicating that GAD is not simply a secondary condition

Epidemiology

Current point prevalence = ~1.6%, lifestime prevalence = ~5%

Median point prevalence in primary care settings is 5.8%: More likely to seek medical attention than individuals with other disorders

Median age of onset = ~31 years oldEarlier onset associated with higher symptom severity, comorbidity, and

vulnerability to other disorders

Women almost twice as likely to meet diagnostic criteria for GADMen have higher rates of comorbid alcohol and substance use Women have higher rates of comorbid mood and anxiety disorders, and

greater degree of disabilityDifferent cultural groups may demonstrate differences in both the content of

worries and focus of GAD symptoms

Etiology: Problem-Solving Ability

Worrying conceptualized as an attempt to anticipate or solve real-life problems (i.e., constructive problem-focused coping)In GAD, the worry process breaks down and becomes pathological

Individuals with chronic worry do not have deficits in problem-solving ability. They have…Less confidence about their problem-solving abilities A negative problem orientation

Negative problem orientation and intolerance of uncertainty predicts worry and symptom severity

Etiology- Probability Overestimation and Catastrophizing

People with GAD exhibit cognitive errors of:Probability overestimation: Thinking a feared consequence

is more likely to occur than it really isCatastrophizing: Assuming that an outcome will be much

less manageable than it actually is

Estimates of the cost of one’s worry (i.e., negative consequences of worrying) correlate with worry severity

Also catastrophize about positive aspects of their lives and hypothetical situations

Etiology- Information-Processing Theories

Greater attention to threatening stimuli, preferentially encode them, interpret ambiguous stimuli as threatening, and memory biases for threatening events

Attentional biases include selective attention toward, difficulty disengaging from, and attentional avoidance of threatening stimuli Attentional bias remains when stimuli are masked;

processing of threat cues may not be at a conscious levelTreatment modifies bias, for example, color-naming

interference is ameliorated by CBT

Etiology: Avoidance Theories

Worry is cognitive avoidance, similar to behavioral avoidanceVerbal worry distracts from full experience of fear (e.g.,

feared imagery, sensations of arousal)Reduction in distress and arousal in the short termWorry is negatively reinforced

Instruction to worry in response to an anxiety-provoking trigger increases threat duration and decreases perceived control Opposite effect of imaginal processing or

relaxation/distraction

Etiology: Intolerance of Uncertainty Theory

Tendency to react negatively to uncertain or ambiguous situations Sometimes prefer a negative outcome to an uncertain oneCauses people to feel less capable of effectively solving

problemsLeads to pathological worry instead of problem solving

Intolerance of uncertainty correlated with worry in GAD and controlsIn CBT for GAD, changes in intolerance of uncertainty

preceded changes in time spent worrying

Etiology: Metacognitive Model of GAD

Metacognition: Thinking about one’s thought processes Type 1 worry: Worry triggered by everyday events (e.g.,

worries about health, safety, or relationships). Type 2 worry: Worry about worry

Positive beliefs: Belief that worry is usefulNegative beliefs: Belief that worry is uncontrollable or

dangerous

GAD individuals hold both positive and negative beliefsMore metaworry than individuals with social phobia, panic disorder,

depression, and OCD

Etiology: Metacognitive Model

Negative beliefsClusters: Worry disrupts performance, worry

exaggerates the problem, and worry causes emotional distress

Associated with pathological worry, even when other kinds of worry and anxiety are controlled

Positive beliefsClusters: Worry helps motivation and worry helps

analytical thinkingUniquely predict pathological worry above and beyond

negative beliefs

Etiology: Emotional Regulation Model

GAD individuals find it difficult to regulate emotional experienceDifficulty naming and understanding emotions, difficulty

accepting emotional experience, difficulty regulating negative emotions

Heightened intensity of emotion strong predictor of GADDifferentiates GAD from social anxiety and major

depressive disorder

Etiology: Emotional Regulation Model

Negative mood states may prevent GAD individuals from using “stop rules” to know when to stop worrying

Example of stop rule: “I will think of as many possible responses as I can to the situation”When the “as many as I can” is paired with negative

mood, person feels she has not generated as many responses as possible after reasonable effort, leading to perseveration

Biological Etiology: GABA Theory

GABA plays inhibitory role in the brain, aiding inhibition of subcortical circuits stimulated by threat GABA receptors dense in frontal cortex, hippocampus,

and amygdala

GAD individuals have decreased GABA activity and less inhibition of these threat-activated structuresAlso, reduced benzodiazepine receptor sensitivity:

important because binding of a benzodiazepine receptor facilitates GABA binding

Benzodiazepines effective treatment for GAD

Biological Etiology: Neuroanatomical

Larger amygdala and superior temporal gyrus volumes, hypometabolisim in the basal ganglia, and hypermetabolism in the prefrontal cortex

Disrupted connectivity of the amygdala with cortical and subcortical regions important for anticipatory anxiety and emotional processingActivation in the prefrontal cortex regulates activation in

subcortical structures Problems in circuit may lead to GAD emotional

processing deficits

Biological Etiology- Other Neurotransmitters Hormones

Neuroephrine (NE): No differences between clinical and control groups found on baseline levels even though selective NE reuptake inhibitors are effective treatment

Serotonin (5-HT): Low levels of serotonin and serotonin receptor dysfunction linked with increased anxiety

Cholecystokinin (CCK): Linked to panic attacks sometimes seen in GAD. CCK agonist induces panic attacks in ~71% of participants with GAD, ~14% of control participants

Cortisol: Levels significantly reduced following SSRI treatment for GAD, and reduced cortisol associated with reduced anxiety

Biological Etiology: Physiological Signs

Chronic worry associated with reduced autonomic variability during stressful tasksLower heart rate variability and decreased

parasympathetic activity during periods of worry and restHeart rate variability is associated with symptom severity

in GAD, but not in other anxiety disorders

Autonomic rigidity leads to less adaptive behavioral and emotional responses to stressful events

Risk Factors: Stress and Family Environment

Stressful life events increase risk of onset and relapseMen with more than three stressful life events

have 8x greater rate of GAD

GAD individuals experience more unpleasant, negative, and rejecting family environments with parent-child boundary problemsPerceived parental alienation and rejection

correlated with GAD symptoms in adolescents

Treatments: CBT

Most commonly used components PsychoeducationRelaxation trainingMonitoring of cues and triggers for worryImaginal exposureIn vivo exposureCognitive restructuring

Treatments: CBT Efficacy

CBT superior to wait-list controls and nonspecific alternative treatmentsEffective for symptoms of worry, anxiety, and depression

CBT and pharmacotherapy’s effect sizes are similarCBT has advantage in long-term maintenance of

treatment gains, patient acceptability, and tolerabilityCBT is also useful in helping individuals discontinue

benzodiazepine medication

Treatments: Recent Advances in CBT

CBT variants targeting intolerance of uncertainty and related cognitionsEffective in group and individual formatsLasting improvements in GAD symptomsGains maintained longer than with relaxation therapy

CBT therapy derived from Wells’s metacognitive modelLasting improvements in GAD symptomsGreater reductions than CBT targeting tolerance of

uncertainty

Treatments: Recent Advances in CBT

CBT augmented with other treatment strategies (e.g., motivational interviewing) may reduce treatment resistance and enhance efficacy

Unclear which components of CBT are most useful and whether new variants are reliably better than standard CBTLarge percentages of clients continue to experience

significant symptoms at posttreatment and follow-up.

Treatments: Pharmacological

Response of GAD to placebo is particularly high (> 40%)More difficult to demonstrate significantly better effects for specific

medications

Serotonin reuptake inhibitors (SSRIs) are the first-line therapy for GAD

CBT and pharmacotherapy similarly effective

Benzodiazepines reduce both somatic and cognitive symptomsPotential tolerance, dependence, and withdrawal symptomsOnly recommended for short-term treatment (i.e., less than 4 weeks),

as an adjunct to antidepressant medication, or for severe, treatment-resistant GAD symptoms

Treatments- Alternative Pharmacological Treatments

Buspirone: Partial agonist of presynaptic serotonin receptors Moderate effect size Less well tolerated in clinical practice and less effective than SSRI treatments

Selective Neuroepinephrine Reuptake Inhibitors (SNRIs) Venlafaxine has moderate effect size (similar effects to paroxetine) Demonstrated effectiveness over longer treatment trials Concerns about its safety in overdose and cardiac implications

Pregabalin: Analogue of the neurotransmitter GABA Small to moderate effect sizes (not approved for GAD in United States) Greater efficacy for treating psychological distress relative to somatic symptoms

Second Generation Antipsychotics Not effective as augmentation in treatment refractory GAD Quetiapine effective as monotherapy. Significant side effects limit clinical utility