A presidential fiat declared “the decade of the brain” in the last decade of the last century. Phenomenal growth in research and understanding of the central nervous system focused on its structure, function, and potentialities, complemented by basic and clinical neurogenetics. This knowledge boom gains shape from the investigative technology at hand, but its organization from existing paradigms brings to mind the tale of the blind men exploring the elephant.
While psychiatry's basic science is neurobiology, research entails a broader field, although neurobiological and nosological initiatives are at center stage. Tried and true psychiatric research initiatives such as epidemiologic studies, descriptive psychopathology, and illness course and outcome studies receive less attention.1 Psychodynamic theory no longer reigns as the predominant organizing theory,2 but there are few bridges between its domain of personal information and neurobiology data.
Thus, psychiatry lacks a clinically relevant integrating framework that is at once comprehensible to the psychiatrist, intuitively acceptable to the public, and scientifically sound. By default, conglomerated advances in neurobiology substitute clumsily for an organizing basic science. Neurochemistry advances correlated crudely with psychopathology allowed emergence of the “biochemical imbalance” reductionistic explanation.
Clinical psychiatry's dramatic transformation stems also from the 1980 third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) and subsequent revisions.3 Earlier manuals used narratives of clinical syndromes that resembled the introductory passages to specific mental disorders present in later editions but lacked a menu-like specificity. The more recent two editions3,4 changed a psychiatry practice already entering a psychopharmacotherapeutic revolution. These changes mostly improved practice, but it may be argued that psychiatry now functions less effectively as a clinical discipline. Downsides of the new era stem less from the documents themselves than from their use. Manual users tend to see entities and their defining criteria as valid clinical diseases or illnesses, rather than at the level of disorder that actually is designated by the manual.
The term “disorder” suggests a complete spectrum from symptom complex to disease. As a categorical framework, DSM defines disorders as separate entities or categories even when they exhibit major dimensional characteristics (eg, attention-deficit/hyperactivity). Partly as a result of the manual's lack of power on dimensional components, users increasingly reach multiple comorbid diagnoses when addressing a patient.5 The original intent of DSM diagnostic criteria involved a need for clinical decision making in epidemiologic and other research projects, rather than for defining clinical caseness.6 As such, clinical parameters such as impairment and “need for treatment” do not have explicit indication in diagnostic categories.
Diagnostic validity requires differentiation of psychopathology from normal states, pathological states that represent statistical variations from physiologic norms, pathognomonic symptom expression, and syndromal patterns.7 These issues confound the application of DSM criteria to clinical cases and, of course, research. From another angle, DSM criteria were not designed for research, or at least not for sophisticated research strategies; clinically, they function as more of a diagnostic “gatekeeper” or screen.1 Unfortunately, present DSM use often entails rigid criteria for diagnosis, not merely diagnostic aids. This stems from the lack of an integrating and organizing basic science for clinical psychiatry.
Child and adolescent psychiatry depends on a developmental perspective that has increasing relevance for general psychiatry. Anna Freud pioneered using developmental lines;10 a sample line has the child moving from dependency to emotional self-reliance and object relationships; another depicts a child's cognitive progression over time. Line elements follow overlapping predictable sequences. Distortions or deviations may lead to psychopathology.
Erikson's similar epigenetic developmental approach included eight stages of intrapsychic-social tension, consolidations of which play crucial roles in optimal personal development.11 Each stage incorporates antecedents from previous stages and, in turn, projects elements to later stages.
The developmental approach applies to biological, psychological, interactive, and environmental factors.12 Developmental discontinuities play roles for clinicians. Evolving biological factors interact with the environment, modifying phenomenology and course over time. Symptomatology may alter normative maturation sequences.13
Advances in the neurobiological sciences, refinement of psychiatric nosology, the biopsychosocial model, and the developmental approach have added to psychiatric practice and patient care. Yet along the way, something went missing. Psychodynamic theory explained human behavior and psychopathology in a comprehensive framework. Its humanistic qualities appealed to practitioners and patients; while it felt compelling and intellectually stimulating, it incorporated a developmental framework, and it dimensionally bridged normality and psychopathology. Dynamic nosologies possessed internally consistent and self-contained features. The model's richness provided the patient and the therapist more with meaning than did oversimplified “chemical imbalances.” Still therapeutically useful, psychodynamic theory nevertheless fails as a basic science framework in light of noted previous advances.2,14 However, although it no longer furnishes organizing principles, nothing has replaced it.15,16
While searching for this elusive framework, we must avoid the traps of self-fulfilling theory-building without empiric testability. The framework must apply equally to biopsychosocial and sociopsychobiological approaches, and it must allow easy movement between levels. Practitioners must comprehend the framework readily, and patients must find it acceptable. It must withstand the rigors of scientific scrutiny, foster research, show clinical practicality, and demonstrate compatibility with psychiatric nosology while bridging pathology and normality. It must define caseness in psychopathology. It must position the specialty in biology as applied in medicine. It should also intellectually enrich and challenge, feel humanistic, and allow for links between humans as biological, psychological, and social with nonhuman biological entities as well as psychological and social system schemata.
We label as the “social brain” the summed synergy of brain circuits mediating social function. This metaphor emphasizes that the brain unique to the human species evolved with characteristics of what has been called the envirome (human environment) represented in brain structures.21 The model also emphasizes that each individual human brain developed with and structurally incorporated its particular envirome; it acknowledges the human brain as a vehicle for conspecific communication among members of the same species.
The social brain idea suggests a scientific utility of finding similarities and contrasts between humans and other animals at multiple levels of systems organization, including developmental sequences.22 It brings ethology and evolutionary science to the specialty.
Applications of evolutionary science to psychiatry include explanations of gender psychological differences, the concept of mind as made up of subsystems that have responded to natural selection for solving specific problem sets, insight into factors contributing to parental violence against children, and hypotheses on specific mental disorders.23 The developmental neuropsychiatric literature includes the suggetion that attention-deficit/hyperactivity disorder represents an evolutionary adaptive response to a certain environmental set (hunting) at the expense of adaptation to other settings (school).24
An anthropological cross-cultural inquiry about socially meaningful rituals and the expression of obsessive-compulsive disorder (OCD) showed parallel symptom content.25 Neuroanatomical modularity of central nervous system circuits seems relevant to OCD expression.19 Such a brain module may stem from selection pressures involving social order, rules, and right versus wrong. Recent work using evolutionary principles applied to developmental psychopathology focused on an “enduring vulnerability” to a number of psychopathological states from highly “conserved behavioral and mental capacities” intrinsic to the evolutionary success of the human species so far.26 Their importance means a low probability of losing these features through evolution.
Applying canalization to early childhood development suggests a species-specific pattern of individual ontogeny in the predictable emergence of cognitive development. For example, canalization might indicate a limited amount of range, patterns, and critical periods in language development exist in children, irrespective of the language spoken.30
The canalization concept allows the envisioning of environment–genome interaction in developing psychopathology.31 A normal interaction of genetics and environment leads to a predictable developmental course, which can be visualized as a groove or ditch created by rainwater runoff. Environmental or biological influences may alter developmental courses so that they diverge from the usual surface grooves. Initial configurations develop in the pathway of the groove, but departure from a typical groove, and the deepening of that groove over time, models the severity and course of psychopathology.
We believe that a social brain analysis may explain a case of a neuropsychiatric developmental disorder. The model incorporates a developmental framework within a neurobiological and epidemiologic point of view, makes use of and fulfills the promise of the biopsychosocial model, adapts the DSM categorical phenomenologic approach to a dimensional perspective, and uses an evolutionary biological perspective, canalization.
This patient, designated NN, remained in our care for more than 20 years. We previously reported his case in tabular fashion as child/adolescent patient number 1 in an article on comorbid Tourette syndrome and bipolar disorder.32 In another aticle on comorbid Tourette syndrome, bipolar disorder, and autism, we reported his history in summary fashion as N.N.33
During the 20 years he was in our care, NN presented a range of longitudinal DSM comorbidities, including autism, OCD, Tourette syndrome, bipolar disorder, and panic disorder. He came to clinical attention at age 6, when his parents reported oppositional behavior, outbursts of temper, and obsessive-compulsive behavior. Born prematurely, he had spent an initial several weeks in a neonatal intensive care unit, surviving two cardiac arrests before his discharge to a foster home, where he may have been neglected during his first 3 months. Other foster placements apparently entailed less neglect, although the timing of developmental milestones remained unrecorded.
NN's mother displayed inadequate nurturing skills, causing him to be adopted by a childless couple at age 18 months. The birth mother, 19 years old at his birth and hearing-impaired, likely from congenital rubella, was alcohol-dependent. Herself a product of a teenage pregnancy, she experienced many informal family placements when she was young, some of them neglectful. NN's maternal grandmother had left school in the eighth grade to work as a waitress and factory worker. NN's 25-year-old birth father abandoned the mother on learning of the pregnancy; his family history thus remains unknown.
NN's adoptive parents, a mother who worked in healthcare and a professional father, noted after adoption that NN exhibited social isolation, verbal nonresponsiveness, gaze avoidance, and lengthy episodes of repetitive rocking behavior. He walked clumsily and displayed some toe walking. He banged his head in the crib and later seemed accident-prone. Severe temper tantrums ensued, with disturbed routines and play that showed ritualistic features and little imagination. At age 2, he displayed minimal language skills and remained largely uncommunicative.
When he was 2, a lower extremity fracture required cast immobilization. During this time, his mother and grandfather spent much time reading to him to soothe him and help fill his days. Even with this intense, enforced interpersonal involvement, he remained emotionally distant. He did not show echolalia or pronomial reversals. At age 35 months, he developed three word phrases. Toilet training occurred at approximately age 4. At about the same time then, he began a stereotypic pattern of running his fingers repeatedly through his hair and sniffing his fingers.
Between ages 4 and 6, while enrolled in a special preschool program, NN made significant developmental gains. Verbal skills improved dramatically, and he reduced irritable and demanding behaviors and showed more active involvement with peers. Prior difficulties with pre-sleep rocking, night terrors, and frequent awakenings remitted. Still, in kindergarten, the teacher noted withdrawn behavior and little initiative; he required other children to participate in an activity before he would join in. The teacher also noted word-finding difficulties.
When NN was seen at age 6, the parents revealed that he often would come home from school with unverifiable tall tales, such as a policeman visiting the class or a robbery occurring in the neighborhood. He immersed himself in fantasies related to the “Star Wars” character Darth Vader. The parents could not always tell if he had crossed a boundary between fantasy and false belief. NN also could be quite affectionate. He usually was easily disciplined, although temper tantrums could follow parental nonresponse to his demands. Very meticulous about his room's arrangement, he compulsively placed his toys and exhibited specific eating and other daily activity rituals.
At this examination, NN appeared older than his actual age due to a large girth and general stature. He exhibited initial and appropriate stranger anxiety, with inhibition of free-flow motor activity, while his motor movements were clumsy, disjointed, and dyspraxic to a degree. He made good eye contact and smiled at times, with no motor or vocal tics. A mild articulation problem complicated his soft, slowly paced speech. His coherent language showed a vocabulary consistent with age. He expressed euthymic affect. Following the interview, but after returning to his mother in the waiting room, he showed whiny annoyance and tantruming. His thinking showed a preoccupation with the playroom's specific rules. His fantasies featured matter-transformation, namely turning water into wine and sandy water into tea. He did running commentary on his actions. Cognitive and educational testing placed him in the average range for intellectual functioning, although he seemed at risk for learning disabilities.
NN's DSM-IV-TR diagnoses at age 6 were consistent with a history of autistic disorder; OCD, with residual symptoms of the repetitive and ritualistic symptoms of autistic disorder as an alternative diagnosis; oppositional defiant disorder; mood disorder – not otherwise specified, manifested through temper outbursts, periods of withdrawal, sleep disturbance, and excessive involvement in fantasy (these symptoms also could have been residuals of autistic disorder and a history of neglect).
When next seen, NN was an 11-year-old sixth grader. He had made significant gains developmentally, showed much more awareness of his surroundings and the social nuances involved therein, while displaying fewer oddities in interpersonal relationships. He progressed in school, with grades of Bs and Cs. He took lessons in tae kwan do.
Perhaps coincident with the birth of a sister when NN was 9, he developed difficulties that interfered with peer and parental relationships, including a pattern of impulsive aggression, often with dramatic and threatening gestures. A rich fantasy life around aggressive themes used popular symbols, such as the soldier of fortune Rambo. Often, he acted out his fantasies with to and fro verbalizations or with stuffed animals. From time to time, his parents would discover him mumbling to himself regarding aggressive fantasies.
NN continued a strong need for order in his environment and exhibited mannerisms, especially his long-standing running of his fingers through his hair repeatedly. Since age 8, he had exhibited a pattern of waxing and waning motor and vocal tics that included blinking spasmodically, licking his lower lip, repeatedly patting his clothing, touching his hair, licking his fingers, rapidly touching his foot, and rocking his body. Phonic tics included grunts, loud unusual noises, loud sniffing, throat clearing, and coughing. He would also mutter and chant to himself. He would ask himself a question and answer it verbally. He also would echo movie dialogue. When under stress, he often repeated the words and actions of the reprimanding person.
He typically slept restlessly, with early awakening followed by rocking. His mood showed distinct changes, at times showing irritability, sullenness, and negativism but at other times exhibiting almost constant rapid speech and exaggerated and expansive physical posturing that accompanied heroic fantasy themes. Periodically, he showed restlessness with easy distractibility. His eating had increased, and he had gained significant weight.
When examined, NN appeared well-groomed and moderately obese. He tended to avoid eye contact, seemed restless and fidgety, and on occasion sniffed his fisted hand in a stereotypic pattern. At times he whispered, and on two occasions he repeated his own phrases. He often lost his train of thought when distracted by elements in his environment and perhaps by his own inner experiences. Otherwise, his thoughts seemed coherent and logical. His affect seemed that of pressured anxiety. He denied depression or elevation in his mood as well as auditory, visual, or olfactory hallucinations, and no paranoia seemed evident.
At age 11, given his difficulties with attention and the affective elements, NN was treated with courses of desipramine and then protriptyline, with psychotherapy follow-up from his referring psychologist. Perhaps enhanced by tricyclic medication, he exhibited significant (and clarifying) symptom changes. He significantly intensified his pressured mood, and as his activity level increased, he became more destructive. With protripty-line discontinuation, mood and behavior returned to baseline, but within weeks, the parents noted alternating periods of irritability, negativism, mood elevation, occasional grandiose thinking, giggling, and hyperactivity. They also noted a preoccupation with germs and dirt and compulsive hand washing, especially after feeding the dog, including forcing other people to wash their hands after they fed the dog.
A sleep deprived sleep electroencephalogram was interpreted as normal. He had normal bone age and a normal thyroid-stimulating hormone.
DSM-IV-TR diagnoses at age 11 were consistent with bipolar I disorder, perhaps amplified by exposure to tricyclic antidepressants; Tourette syndrome, perhaps enhanced by exposure to tricyclic antidepressants; OCD; and history of autistic disorder.
Psychotherapy continued. His parents noted preoccupation with televised professional wrestling, he became aggressive with the family dog, and to his parents' chagrin, he attempted twirling around and body-slamming his younger sister. Along with heightened affect, vocal tics increased and fluctuated with his hyperthymic intensity. Lithium treatment and attaining levels in the higher therapeutic range fostered mood stability; he also slept better. Although less physically aggressive with his sister, he still teased her. Tics diminished, and compulsive hand-washing lessened. Symptomatic fluctuations persisted, but overall he did better.
Ages 13 to 17
When NN was 13, lithium-induced nephrogenic diabetes insipidus caused drug discontinuation. Treatment then with clonazepam targeted mood stability and the tic disorder. It worked less effectively than lithium, so lithium was tried in combination with a thiazide diuretic complemented by the clonazepam. This resulted in tolerable polyuria, while again improving his tics, mood, sleep, and behavior. When he was 14, a full-scale IQ of 106 included subtests that reflected learning disabilities. At age 15, projective psychological testing inconclusively suggested bipolar disorder. School grades included Bs, Cs, and Ds.
At age 15, a first psychiatric partial hospitalization occurred after he picked a fight with another boy in school while exaggeratedly laughing and insulting others. Suspicious, he wished to take a knife to school for protection. He proclaimed Ninja status and suggested he'd “torch” his sister's room. When upset at home he banged on the walls.
At age 16, inpatient psychiatric care stemmed from symptoms of increasing irritability, threats to hurt others, and grandiosity. He hurt his sister by pushing her face to the floor, swore at his parents, threatened others with a closed fist, and may have made a bomb threat at school. By now, tics were minimal, with no distinct obsessions or compulsions. Lithium and clonazepam had been discontinued, with carbamazepine substituted. On examination, he show no overly active behavior, no motor nor vocal tics, no obsessions nor compulsions, and no overt paranoia. Speech was pressured but logical, but future plans indicated grandiose thinking.
At this age, DSM-IV-TR diagnoses were consistent with bipolar I disorder, Tourette's syndrome (in remission on medication), and history of OCD and autistic disorder. Treatment included a combination of clonazepam and carbamazepine, in addition to psychotherapy.
At age 17, NN showed active interest in girls, and in school tried to impress them by declaring himself a wrestler. He signed school papers with the moniker of a popular wrestling star and rationalized it by declaring it a joke. By now, NN had been provided with an individualized education plan for students with serious emotional disturbance. He became more purposely negative to his parents, threatening to turn them into protective services if they did not conform to his demands.
After discontinuing clonazepam and carbamazepine, a trial of divalproex resulted in more calmness and better sleep; he reported no racing thoughts, did not show irritability or explosiveness, and responded reasonably well to curfews at home. Although preoccupied with a famous mafia gangster then in the news, he did so in a more socially acceptable, joking manner. He showed compliance with medication, kept up schoolwork, and planned to move out after high school graduation. He then moved to a neighboring community for technical school. He had his own car and managed his own funds from Social Security disability, for which he qualified.
Ages 19 to 20
At age 19, after a few years of doing well, NN discontinued divalproex, no longer feeling the need for it. He had left technical school, had a brief engagement with a 16-year-old girl, and continued to live independently, with occasional brief periods of depression. In light of his overall developmental history, chromosomal studies including fragile X were conducted, with normal results. For the brief episodes of racing thought, he took clonazepam intermittently.
At age 20, NN felt plagued by panic attacks; these often took him to the emergency department and resulted in brief, usually overnight, psychiatric hospital stays. He frequently called the police, summoning them to take him to the emergency room. He bragged about a special relationship with police. Divalproex, along with lorazepam, treated his panic attacks. Due to fluctuations into depression and the presence of panic attacks, outreach services accessed through the local mental health center prescribed paroxetine for him. He denied use of alcohol or illicit substances, and drug screens were negative. In spite of these interventions, he still overused emergency medical and law enforcement resources, and still felt a special bond between him and certain officers.
On examination during a hospitalization at age 20, NN seemed alert with no motor or vocal tics, but tense and restless. He spoke rapidly with irritability. His speech emphasized achievements and seemed unduly optimistic while lacking insight into his difficulties. He denied depression, suicidality, hallucinations, or delusions. He also denied obsessions or compulsions. DSM-IVTR diagnoses would be consistent with panic disorder without agoraphobia, bipolar I disorder, and history of Tourette syndrome, OCD, and autistic disorder.
Ages 21 to 25
At age 21, NN still frequently visited the emergency department after panic attacks. He received a modest income from his disability payments and was of legal age, so he began drinking alcohol and increased his already prodigious appetite. Younger roommates exploited him as an alcohol source. He and they engaged in immature behaviors while likening themselves to a stylized gang. In actuality, the social skills of the street were far beyond NN and these friends.
During this period, NN only sporadically and infrequently involved himself with psychotherapy. Medications began to include divalproex, lorazepam, and imipramine, and for a time, NN felt less anxious and no longer made police calls while panicked. On examination at age 21, NN related calmly, seeming relaxed with no motor or vocal tics. Affable, his thoughts seemed clear though egocentric. His affect seemed midrange, with the exception of significant anxiety when in the midst of panic.
By age 25, NN had worked briefly in a variety of settings. Typically, he would fairly rapidly lose a job secondary to problems with social skills. When he was 23, he met a young woman with whom he lived for a time and to whom he subsequently became engaged. However, frequent arguments strained the relationship and she ended it. The girlfriend said she felt intimidated by NN because by this time he was more than 6 feet tall and weighed more than 400 pounds.
Hospitalization overnight ensued after he expressed rage, feeling the impulse to go to his apartment to destroy it; he also wished to see his girlfriend, who was then moving from their relationship. NN experienced acute and marked depression, mentioned persistent suicidal ideation, and indicated he would have killed himself but was too busy to do it. His parents provided significant support to him during this time.
On hospital examination, NN seemed alert with good eye contact that felt meaningful. His thoughts seemed coherent and his affect subdued. He admitted depression and worry as well as persistent suicidal ideation, but without a plan. He denied hallucinations and delusions and showed no cognitive delay or tics.
NN subsequently transferred his care to another agency, so no further contact ensued.
NN began life with a number of risk factors as a premature infant who had suffered two cardiac arrests.34,35 He also may have had prenatal alcohol exposure, which predisposes to neurodevelopmental defects and subsequent cognitive and social problems.36 He suffered early emotional deprivation and possible nutritional deprivation, with their concomitant negative effects on cognitive development and the ability to form stable attachments. He required separation from his primary caretaker with the termination of her parental rights. He also had a first-degree relative familial risk for alcoholism and bipolar disorder. Positive factors included his removal from a noxious environment at a young age, with adoption by an educated couple stable in family structure and dedicated to him throughout his troubled development, including the continuing mental healthcare required.
We diagnosed NN's earliest symptoms as expressing a pervasive developmental disorder, namely autism. Given his history of grossly pathogenic care, coupled with his positive outcome for a person with autism, the retrospective question arises now of a possible reactive attachment disorder. He did meet formal diagnostic criteria for autistic disorder with significant impairment, which preempts the diagnosis of reactive attachment disorder. Nonetheless, his deprivation may have enhanced any underlying vulnerability to autism. If we assume a modest vulnerability and a time-limited enhancement of that vulnerability, we might predict a better than expected outcome.
At age 2, NN was a virtual captive audience to his mother and grandfather, who spent long hours reading to him. The forced social contact and exposure to verbal stimuli may have affected his outcome positively. Between ages 4 and 6, he showed significant improvement both symptomatically and developmentally. Strictly speaking, we could have continued with a diagnosis of autism, while interpreting the transformation of his repetitive and stereotypic behaviors and need for routine to comorbid OCD. In the current nomenclature, a diagnosis of residual autism is not available. We tried to reflect this transition by diagnosing NN with a history of autism.
We can make a similar point regarding NN's autistic stereotypic behaviors, in particular his fingers through the hair and finger sniffing, and the later emergence of the tics of Tourette syndrome. The presence of Tourette syndrome may have reflected positive prognostic factors regarding his autism, although this represents a controversial point.37–42 Onset of NN's OCD preceded the onset of Tourette syndrome by 4 years, contrary to the usual sequence of emergence of these often co-occurring conditions.
In terms of longitudinal comorbidity, NN manifested greater than chance concurrence for autism plus Tourette syndrome, Tourette syndrome plus OCD, Tourette syndrome plus bipolar disorder, and Tourette syndrome plus bipolar disorder plus autism.32,33,40,43 During the more active phase of NN's tic symptomatology co-occurring with bipolar disorder, we noted a previously seen pattern: tic severity covaried with the intensity of the hyperthymia and improved with lithium therapy.44
With NN, we have had the rare opportunity of a 20-year continuing care relationship and follow-up of a complex neurodevelopmental neuropsychiatric condition. The Figure (see page 846) shows the ontogeny of his condition as reflected in the longitudinal comorbidities of his DSM diagnoses. Actually, however, the symptom residua of one diagnostic entity may become the symptom antecedent of a subsequent diagnostic entity or entities. As such, the timing of onset or of offset of NN's DSM diagnoses are arbitrary.
Active phases of NN's DSM-IV-TR disorders.
We have already made the case for diagnosis of a history of autism. The Figure shows the sequence of NN's meeting DSM criteria for disorder onset through no longer demonstrating the range of symptoms required for the diagnosis. We propose that the sequence of progression of NN's comorbid diagnoses reflects the developmental course, or epigenesis, of some specific symptoms comprising the phenomenology of syndromes.
Rapoport and Fiske19 noted that obsessive-compulsive symptoms help the process of selecting and controlling actions, ideas, or concerns. For NN, content seemed involved with boundaries, order, rules, right, and wrong — socially directed themes. When very young, he showed social isolation, rocking, and other repetitive, stereotypic behaviors, as well as ritualistic, unimaginative play, all of which qualified him for the diagnosis of autism. As time passed and social involvement ensued, however, stereotypic behaviors lessened, and his room arrangement commanded his attention; he compulsively arranged toys and ritualized his daily routines with preoccupying ego-syntonic aggressive fantasies. Preoccupation with germs, dirt, and hand washing soon followed. Televised professional wrestling fascinated him along with other heroic themes. At age 15, however, obsessions and compulsions disappeared.
We suggest a psychopathological developmental line of repetitive and stereotypic behavior and concerns of his autism with the ritualistic and obsessive behaviors of OCD. Not surprisingly we discern a similar pattern with his tic symptoms of Tourette syndrome; many see Tourette syndrome as an alternate expression from OCD of a common genetic diathesis.45 Again we note NN's early rocking, other stereotypies such as the running of his fingers through his hair followed by finger sniffing, and later development of simple motor and vocal tics, including a persistence of fingers in the hair and finger sniffing. He would mutter and chant to himself. He exhibited echolalia, reflecting a complex vocal tic, although echolalia also is associated with autism. His physical posturing appeared expansive at times, and by later adolescence, NN's tics went into abeyance, consistent with the developmental course of this condition.40 We hypothesize a neuropathological developmental line of his autistic stereotypies with the tics of his Tourette syndrome.
Might we similarly trace the symptomatology of NN's bipolar disorder? After an autistic stance, he went through a phase of exhibiting demanding, irritable behaviors; as a school-aged boy, he told tall tales, and his circumscribed interests often included grandiose fantasies in which he attributed to himself magical powers. His repetitive mumblings often included aggressive fantasies. He became hyperverbal and expansive, and as a young teenager, he became suspicious of others and wanted a knife at school for protection. As time passed, grandiose ideas were reframed to joking.
We hypothesize a psychopathological developmental line for NN's bipolar disorder, particularly the manic symptoms. Namely, autistic isolation transmuted to difficulties with affect regulation, and obsessional thoughts transmuted to grandiose ideation, mediated by content of his thought. Tic-like repetitive mumblings may have given way to hyperverbal speech.
As an adult, NN's major psychopathological symptoms took the form of panic disorder. We hypothesize common roots with the isolation and catastrophic responses of his autism. The need for order and control of his OCD may have transmuted to feelings of loss of control of his panic symptoms. The spasmodic and interruptive nature of his tics may have been reflected in the interruptive process of his panic attacks. The paranoid ideation of his bipolar disorder may have manifested as part of the determinants of his anxiety. It has been suggested that, in some cases, patients with bipolar disorder and panic disorder may be reflecting a shared genetic vulnerability for both disorders.46,47 For NN's panic disorder, we hypothesize a psychopathological developmental line with his autism, OCD, Tourette syndrome, and bipolar disorder.
We previously had applied the evolutionary concept of canalization to our understanding of the neuropathology and psychopathology of Tourette syndrome.48 Tourette syndrome is a developmental neuropsychiatric disorder defined by the presence of multiple motor and vocal tics with a duration of at least a year and an onset by age 18. Much evidence suggests striatal dysfunction in Tourette syndrome. Genetically, it seems a heterogeneous condition. People with Tourette syndrome demonstrate a greater than chance concordance for attention-deficit/hyperactivity disorder, OCD, pervasive developmental disorders including autism, and bipolar disorder.32,40
We suggested that, for patients with comorbid Tourette syndrome and autism, expression of Tourette syndrome may reflect a point of neurodevelopmental confluence through which a number of etiologically heterogeneous neuropsychiatric and neurodevelopmental processes must pass as a function of development. This point of confluence was hypothesized to be determined by the canalization of developmental process and by the canalization of deviations or distortions from that process.40 We made a similar case for the likely greater than chance concordance for Tourette syndrome and bipolar disorder.32 Additionally, we hypothesized a deep canalization for normal striatal function. Resulting from this, a variety of perturbations to striatal function would lead to a limited array of deeply canalized neurophysiological and symptomatic manifestations; a gradient of the depth of dysfunction might exist within that array. Statistically, the more deeply canalized dysfunctions would appear more often in conjunction with the less deeply canalized dysfunctions.
In addition to explaining resistance to variation, canalization infers a model of diagnosis-specific risk at the juncture between environmental and genetic factors.40 We hypothesized that Tourette syndrome is reflective of deeply canalized striatal dysfunction and would be highly likely to appear as a product of a variety of perturbations to the corpus striatum. This would account for the genetic heterogeneity of Tourette syndrome and for the greater-than-chance concurrence of Tourette syndrome with a number of conditions that are mediated by striatal dysfunctions.
We have presented our hypothesis of canalization in Tourette syndrome essentially as a linear model. However, our descriptions of “perturbation” of striatal function in Tourette syndrome is consistent with concepts of general systems theory. It is likely that nonlinear dynamics also influence Tourette syndrome and its comorbidities with all their complexities.49
For NN, we believe that the epigenesis or developmental line of his psychopathology can be combined with the concept of canalization. We hypothesize that the implementation of neuroanatomic structures and neurophysiologic functions, perhaps in the form of neural circuits, served as later blueprints for the contemporaneous sequential expression of his psychopathology. This hypothesis reverberates with the insights of John Hughlings Jackson regarding the evolutionary patterned hierarchical organization of the central nervous system, with lower centers being more predictable in effect and under the influence of higher centers.50,51 During the course of evolution, there can be just a limited range of departure from neuroanatomical structures and neurophysiologic functions that are more highly canalized. Consequently, there is a limited range of the sequencing and expression of normal behavior and of psychopathology as an emergent of how those more highly canalized structures and functions have become configured. Thus, it is probable that perturbation of function in a specific area of the brain will lead to a more or less limited range of psychopathology, with some expressions of that psychopathology being more likely than others. The form and expression of that psychopathology also will be determined by the envirome incorporated over time and by the ontogenesis of the brain.
In NN, we hypothesize that the striatum served as the point of confluence of perturbation affecting different neural circuits incorporating striatal activity. This contributed to the diathesis for the specific comorbidities expressed: autism,52,53 OCD,54,55 Tourette syndrome,56,57 bipolar disorder,58,59 and panic disorder.60,61 Influenced by neurological and psychosocial development, the result was a hierarchical and longitudinal pattern of comorbidities — that is, autism, OCD, Tourette syndrome, bipolar disorder, and panic disorder, in that order.43,62 In other words, the range and probabilities of psychopathological expressions within specific enviromes is just as determined by evolution and intrinsic to brain neural circuitry as are the range and probabilities of normal behaviors.