Chapter 14 Sinistrality and Psychopathology

LEFT-HANDEDNESS Behavioral Implications and Anomalies, S. Coren (Editor) 0 Elsevier Science Publishers B.V. (North-Holland), 1990

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Chapter 14

Sinistrality and Psychopathology Pierre Flor-Henry Alberta Hospital and University of Alberta The patterns of cerebral organization which determine sinistrality, although partially understood in certain instances, remain obscure and enigmatic in others. A variety of psychopathological disorders are associated with an excess of lefthanders in the afflicted individuals: autism, certain forms of schizophrenia, bipolar (but not unipolar) affective illnesses, susceptibility to dysphoric mood states, certain types of criminal psychopathy (particularly if recidivistic) and epilepsy with psychosis. Intellectual retardation is also associated with increased sinistrality: Bradshaw-McAnulty et al. (1984) for example found that right hand preference varied inversely with the severity of the mental retardation. Pipe (1987) reported that the incidence of nonright-handedness in developmentally retarded individuals and in patients with Down's syndrome is approximately twice that of a normal comparison sample. Subsequently Pipe (1988) reviewed the evidence which shows that the excess sinistrality in Down's syndrome cannot be the result of "pathological left-handedness:" left hemisphere damage evoking compensatory sinistrality, since in Down's syndrome, as in infantile autism, the subjects with increased right hemisphere language functions indicated by left ear superiority on dichotic listening are dextral. The same unusual association has been found in autistic children (Prior and Bradshaw, 1979). That the pathological left-handedness hypothesis has to be applied with circumspection in special pathological populations is further shown by the fact that increased sinistrality occurring with mild mental retardation is linked to increased familial sinistrality (Searleman et al. 1988). Taylor (1975) in his study of temporal lobe epileptics who underwent temporal lobectomy notes a significant excess of

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sinistrality in the group as a whole (20%), an effect for which patients with “alien tissue” lesions arising during embryogenesis were responsible (28% sinistral), rather than subjects with post-natally acquired mesial temporal sclerosis (12% sinistral). Moreover as he remarks “It is hard to relate this to ‘pathological sinistrality’ (Satz, 1972), since it was equally likely whether the lesion was in the left or right temporal lobe.” At the same time there are undoubtedly some populations where sinistrality, compensatory to left hemisphere pathology, arises. Vargha-Khadem et al. (1985) investigated the consequences of unilateral brain disease, acquired pre- and/or post-natally in 28 children with left hemisphere pathology, 25 with right-sided lesions, comparing these two groups with each other and with 15 normal children. Whereas 100% of the children with right hemisphere lesions were dextral 87% of the patients with left hemisphere lesions were strongly left-handed and all patients with prenatal or early post-natal left hemisphere lesions (two months to five years) were strongly left-handed. The familial incidence of sinistrality was similar in the left and right brain-damaged groups (29% vs 38% respectively). The theme of this paper is psychopathology. However it is important, in order not to lose sight of the complexity of the issues raised by the sinistral brain, that its correlates can be with intellectual-cognitive or manipulo-spatial superiority. Hicks and Dusek (1980) observed that gifted childrm (I.Q. 132 or higher) were significantly less dextral than non-gifted children (I.Q. 132 or less). The fact that Leonard0 da Vinci was left-handed is well known. Perhaps even more remarkably the greatest violinist of all times, Paganini, even although he played the instrument as if he was right-handed, was also left-handed. The number of geniuses who were left-handed is quite extensive, for example, the painters Michelangelo, Rapheal, Holbien, Picasso; in music C.P.E. Bach and Raveli; in the performing arts Charlie Chaplin, Greta Garbo, Marcel Marceau, and Harpo Marx; and political leaders include Alexander the Great, Charlemaine, and Napolean Boneparte. Hkcaen (1984) cites astonishing figures on how, in unimanual sports such as fencing or tennis, the top positions at the level of world or Olympic competition are dominated by sinistrals. In 1981 the 20 tennis players classified as best in the world included 25% of sinistrals. The top 8 places in the Mexico games of 1979 for fencing were all won by sinistrals; the same was true in the Moscow Olympics of 1980. Further in both these sports the number of sinistrals increases proportionally with ranking: for tennis in 1980 there were 17% sinistrals in the first 200, 24% in the first 25, 40% in the first 10 and 75% in the first 4. For fencing in the same year 48% in the first 25, 80% in the first 10 and 100% in the first 4! Similar trends were observed in the world championships for fencing, 1981.

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Turning to neurological diseases there are curious observations where in some cases sinistrals are at an advantage, others at a disadvantage: early onset primary degenerative dementia of the Alzheimer type (onset before 65) affects selectively the left hemisphere, compared to the right and the prevalence of left-handedness in this group is 22%. This contrasts with the late onset senile dementias in whom there is an excess of dextrality (Seltzer et al. 1984). On the other hand (no pun intended!) in schizophrenic patients sinistrality protects against the emergence of persistent tardive dyskinesia (Barr et al. 1989).

Sinistrality and Psychosis Taylor (19 5) extracted from a series of 255 patients H.-O ..ad undergone temporal lobectomy for the relief of intractable psychomotor epilepsy all the patients with ‘alien tissue’ (small tumours, hamartomas, focal dysplasias) and compared them with all the cases of mesial temporal sclerosis. There were 47 of the former and 41 of the latter. Complex interactions between type of neuropathological lesion, sex, handedness and laterality of the epilepsy significantly determined the probability of psychosis which, characteristically, was high in the total sample since 13 of the 88 subjects exhibited a schizophrenic disorder (15%). The probability of psychosis was highest in females, with left sided epilepsy, who were sinistral and who had alien tissue neuropathology. Dextral males with right hemisphere epilepsy and mesial sclerotic lesions were least susceptible to a psychotic evolution. 7 of the 13 psychotics, or almost 54% were left-handed. The five published series where handedness frequencies are considered all show a remarkably high frequency of sinistrality in the special group of schizophrenias associated with temporal lobe epilepsy. The range of sinistrality in the schizophrenic psychoses of TLE lies between 17% and 71.4%, as opposed to 5.3% and 14.6% in control groups: temporal lobe epilepsy without psychosis (Taylor, 1975; Kristensen and Sindrup, 1978; Toone and Driver, 1980; Sherwin et al. 1982; Trimble and Perez, 1982). These several studies cumulate 179 epileptic schizophrenics, with an overall sinistrality of 22.3% whereas for the 238 controls the overall sinistrality was 9% (see Table 1). There are important conclusions which emerge from a consideration of those variables which determine a schizophrenic evolution in temporal lobe epilepsy. As table 1 illustrates sinistrality plays a part, but cannot be necessarily attributed to “simplistic theories of the genesis of left-handedness,” as Taylor repeatedly

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Table 1: Sinistrality in temporal lobe epilepsy with psychosis Author

Psychotic

Controls

%

n

total n

%

n

total n

Taylor, 1975

53.8

7

13

14.6

11

75

Kristensen & Sindrup, 1978

17.6

16

91

5.3

5

95

Toone & Driver,l980

17.0

10

57

-

Sherwin et al.1982

71.4

5

7

7.3

5

68

Trimble & Perez,1982

18.0

2

11

-

40

179

21

238

Total n Overall sinistra 1

22.3%

8.8x

emphasises (Taylor, 1975, 1977) in spite of the fact that left hemisphere epilepsy is here another crucial determinant of psychosis. The observation that lesions of the dominant hemisphere arising during embryogenesis, rather than thoseoccurring post-natally are responsible for a later psychotic evolution emphasises the importance of the developmental epoch at which pathological events disrupt the organization of the central nervous system. It is not only what happens where in the CNS which influences subsequent (dis)organization sometimes after a prolonged latency - but when it happens which may be the factor of overriding importance. The onset of seizures with mesial sclerosis is earlier - mostly before the age of two - in contrast to the alien tissue lesions which lead to seizures manifested for the first time much later - after the age of 10. Furthermore there is evidence that those temporal lobe epileptics who subsequently become psychotic have a tendency to first manifest their seizures during puberty: another critical developmental period which, of course, is also shared by the endogenous schizophrenias. It has been shown, formally, that the mental symptomatologyis identical in "epileptic"and "endogenous"schizophrenia (Perez and Trimble, 1980). A substantial body of evidence confirms that schizophrenia is associated with increased incidence of sinistrality. Indeed, although much less studied, this also appears to be true for bipolar affective syndromes. Let us exami9e the evidence for schizophrenia first. One of the first studies, with an impressive

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sample size, is that of Dvirsky, (1976) in the U.S.S.R. He compared 660 male and 610 female schizophrenics against 2,150 healthy male and 2,190 healthy female controls. The continuous forms of schizophrenia were associated with a significant increase in sinistrality. The effect was more pronounced in males than in females, and left-handedness was associated with the more malignant forms of the illness. Dvirsky concluded that sinistrality in schizophrenia was a modifying factor that carried the probability of increased severity of illness. In a later investigation (Dvirsky, 1983) 1,177 right-handed and 93 left-handed schizophrenics were compared in order to establish the possible relationships existing among handedness, age of onset and form of illness in these patients. In dextrals the age of onset was later, around the ages of 35-44 with a high incidence of psychoses with cyclothymic and/or affective delusional features, or catatonic episodes - schizophrenic psychoses with intermittent or only moderately progressive course which the Soviet classification labels "shift-like'' forms. In sinistrals the onset was earlier, around 20-24, with a high prevalence of progressive paranoid forms of chronic schizophrenia. Related findings are reported by Katsanis and Iacono (1989) in the study of 63 schizophrenic patients, of whom 56 were male, where 12 (or 19%) were left-handed. A systematic comparison of ventricular size and neuropsychological performance of the sinistral and dextral schizophrenics showed that the left-handed patients had significantly larger lateral ventricles and were significantly more impaired on the Wisconsin Card Sorting test as well as scoring significantly lower on the WAISR IQ than the right-handed schizophrenics. In the United States Gur, (1977) compared 200 schizophrenics with 200 controls and found an excess of lefthanded responses in the schizophrenics. Eye acuity, eye dominance and handedness-footedness were independent measures which showed no significant associations in either the schizophrenics or the normals. In a series from the United Kingdom, (Fleminger et al. 1977) 800 psychiatric patients and 800 controls were studied. The psychiatric group included 102 schizophrenics and 120 affective psychotics. There were significantly more dextrals (consistent dextrality according to Annett, 1970) among female psychotics than controls, with a similar tendency towards increased dextrality in male psychotics. There were significantly more left-handed writers in male than in female schizophrenics and more mixed-handedness (right hand preferred for writing with left hand responses in one or more of the 12 items of hand preference) in women with personality disorders. Taylor et al. (1980) replicated these results in a sample of 272 schizophrenics who exhibited a significant excess of dextrality (consistent) when compared to the 800 controls of Fleminger et al. (1977). In a subsequent

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study Taylor et al. (1982) reanalysed the Fleminger et al. (1977) investigation by applying the actual Annett handedness classification instead of the Fleminger modification which had been utilized in the earlier reports of this group. Then, the excess dextrality in the functional psychoses was no longer significant. With respect to schizophrenia, the males now showed a trend towards excess sinistrality and the females towards excess full dextrality. Nasrallah et al. (1981) examined 79 consecutive male patients between the ages of 18 and 50, admitted to an in-patient unit over a period of one year and who satisfied DSM-I11 criteria for schizophrenia. They were compared to a control group consisting of 75 hospital staff members. There was a significant excess of sinistrality in the schizophrenic patients (19%) compared to the controls (5%). Paranoid schizophrenia had significantly more left-handed subjects (33%) than nonparanoid forms of schizophrenia (11.5%). Nasrallah and McCalley-Whitters (1982) found no difference in handedness in 88 manic patients (all males) compared to 86 age and sex-matched normal controls (8 and 7% sinistrality respectively). Piran et al. (1982) reviewed the handedness and eye preference in 25 early onset schizophrenics (average age 18 years), 24 brain-damaged subjects, 16 non-psychotic psychiatrically disturbed subjects and 16 healthy controls. All groups were comparable in age and 77% of the schizophrenics were males, the psychiatric controls having an excess of females and the other two groups a sex ratio around unity. With 23% sinistrality for writing and 73% left eye dominance the schizophrenics were significantly more sinistral than all other comparison groups (i.e. 11% left-handed for writing and 27% left eye dominance in the healthy controls, with the other two groups showing lower values). Luchins et al. (1979) found 17% non-dextrals in 66 schizophrenic patients. The full dextral patients were significantly more chronic than the sinistrals. Luchins also administered the Torque test to a subgroup of 55 of these patients. In this test three circles are drawn with each hand. Torque is present when the circles are drawn clockwise with either hand. Torque is associated with sinistrality and, in disturbed children, with a later predisposition to schizophrenia (Blau, 1977). All 34 schizophrenics without torque were chronic whereas the six acute patients all showed Torque. Kameyama et al. (1983) reported on almost 600 Japanese schizophrenics who were diagnosed according to Research Diagnostic criteria. No difference from normals in terms of hand preference was found although the younger patients had a significantly higher frequency of right eye dominance than age-matched controls. Taylor et al. (1983) had also observed a significant excess of consistent dextrality in a combined sample of 179 male prisoners (personality disorders, neurotic and

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violent) as well as in 34 male schizophrenics. In an investigation carried out in the People’s Republic of China (Yan et al. 1985) we found a significant excess of non-dextrality in 200 schizophrenics (20%). This was true for both male and female patients when compared against 432 healthy controls in whom the incidence of non-dextrality was identical to that of Western populations (7%) when cultural variables were taken into account (very strong pressure in China to impose the right hand for writing and chopstick use irrespective of innate preference). The pattern of hand preference in 56 manic-depressive patients did not differ from the controls. The manic-depressives and the schizophrenics had a significant excess of left eye dominance and an increasing divergence between eye and hand dominance when compared to the controls. Andreasen et al. (1982) had found 15% sinistrals in a cohort of 51 schizophrenics. However positive symptomatology schizophrenia was 100% dextral, whereas negative symptomatology schizophrenia was significantly non-dextral, with only 67% dextrality. Furthermore the sinistrals in this series had a significantly greater degree of ventricular dilatation than the dextral schizophrenics (Andreasen and Olsen, 1983). Table 2, which summarizes the evidence reviewed shows clearly that, not withstanding four studies finding excess dextrality in schizophrenia the implications of which will be discussed later, a significant association with sinistrality emerges overall. If the schizophrenic syndrome or bipolar affective disorders are correlated with the sinistral pattern of brain organization it might be expected that mental symptoms might themselves show significant associations with sinistrality or dextrality. There is evidence that this is, indeed, the case. In 70 psychotics, irrespective of diagnosis, Lishman and McMeekan (1976) found a strong association between left-handedness and delusions, a negative association with hallucinations and an over-representation of young males. Pogady and Friedrich (1975) reported an excess of sinistrality in a representative sample of 650 psychiatric patients in a psychiatric hospital: 20% were sinistral or ambidextrous. Paranoid delusions and incoherent thinking were more frequent in sinistrals than in dextrals or ambidextrous patients, whereas emotional lability, depression, visual-auditory hallucinations and obsessions were more frequent in ambidextrous subjects. Manschreck and Ames (1984) found that anomalous motor laterality was significantly higher in schizophrenics than in affectives or normals and very strongly correlated with thought disorder and neurological deficits. These consisted principally of sensory errors on the right side of the body. Further thought disorder and right sided graphesthesia were strongly associated. Manoach et al. (1988) examined the relation between language dysfunction

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Table 2: Sinistrality in schizophrenia: Representative research Schizophrenia Sin istra 1 total n % n

Study

Norma 1 s Sinistral

total n

%

n

225

20

45

432

7

30

1,270

7

93

4,340

4

175

102

13

12

800

15.4 107

66

27

11

**(Chaugule and Master, 1981) 93

68

63

150

50

76

Nasrallah et al. 1981

79

19

15

75

5

4

Andreasen et al. 1982

51

15

8

Piran et al. 1982 (early onset)

26

23

6

16

11

2

Taylor et al. 1982 (Maudsley sample)

26

15

4

Kameyama et a1 . 1983

584

15

86

686

18

121

**Gur, 1977

200

70

139

200

56

112

Manoach e t al. 1988

58

Yan et al. 1985 Dvirsky, 1976 Fleminger et al. 1977* Luchins et al. 1979

Totals

2,487

X2 = 60.03

*

**

31 12%

18 298

6,349

7%

439

( p <0.001)

Handedness as reclassified according to Annett (Taylor et al. 1982) Excluded from overall analysis since classifications that find 50% or more sinistrals i n normals are not satisfactory

(verbal incoherence, derailment, illogical thinking, poverty of information in speech and neologisms) in 58 male schizophrenics. 31% of the sample was lefthanded for writing. All the left-handers were thought disordered, but only 70% of the dextrals, a significant difference at the p ~ 0 . 0 2level of probability. Although the various measures of thought disorder were highly intercorrelated, dextrals and sinistrals did not differ for the items of illogical thinking and neologisms. Some studies, which will be discussed later, also indicate that sinistrals have increased mood instability and are more prone to anxiety than dextrals.

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Sinistrality in Autism and Childhood Schizophrenia Profound affinities link the autistic and schizophrenic syndromes: in both there is a striking excess of males, in both there is an over-representation of first and last-born in the sibship, in both vestibular abnormalities are found, in both there is an excess of sinistrality and in both there are genetic-constitutional (‘idiopathic’) and acquired forms. Satz et al. (1985), who discuss handedness subtypes in autism, review twelve studies published after 1975 which indicated that the prevalence of manifest sinistrality across the twelve studies was 34%. In their own investigations they observe 20% sinistrality and 40% non-dextrality (mixedhandedness). Walker and Birch (1970) studied lateral preference and right/left awareness in 80 male schizophrenic children between the ages of eight and eleven and found an enormous increase in sinistrality. Eighty percent of normal children of comparable age and IQ were right-handed, compared with only 32% of the schizophrenic children, who, in addition, had impaired right/left orientation. Many investigations have noted a striking excess of sinistrality in autistic children; for example, Colby and Parkinson (1977) showed a frequency of 65% non-dextrality in 20 autistic children compared to 12% in normal children. High functioning autistic children have been found to have a specific decrement in verbal, as opposed to performance, subtests of the Wechsler Scales and to exhibit a significant impairment in the left hemisphere in neuropsychological testing, scoring in the normal chronological age level for right hemisphere indicators (Hoffman and Prior, 1982).

Sinistrality in Monozygotic and Dizygotic with Schizophrenia Boklage (1977) analyzed concordance for schizophrenia and handedness in those published twin series that gave the information. In dextrals, if both twins were dextral and one schizophrenic, the probability of concordance for schizophrenia was of the order of 90%. If the twins were discordant for handedness however, the concordance for schizophrenia fell to about 25%, and then the sinistral twin was likely to be schizophrenic, with a milder illness than that occurring in dextral monozygotic twins. Boklage notes that monozygotic twinning is itself an anomaly of embryonic symmetry formation, which takes

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Table 3: Autism and childhood schizophrenia Normals S inistra 1

Schizophrenia S in ist ra 1 Study

total n

Walker and Birch, 1970 80 Colby and Parkinson, 1977 20 Satz et al. 1985 387 (Average across 12 studies)

%

n

68x 54 65% 13 33.6x 130

total n 69 25

%

n

20%

14 3

12%

place extremely early in ontogenesis, before amniogenesis, some 8 or 9 days after conception, with the appearance of the prochordal plate and primitive streak, which define a dorso-ventral axis, thus an antero-posterior gradient, and therefore, right and left. Boklage concludes that abnormalities of embryonic symmetry development are reflected simultaneously in the twinning process itself, in the abnormal motor laterality found in all monozygotic twins (schizophrenic or normal), and in the etiology of schizophrenia in this population. Incidence of sinistrality was 12% (8/66) in dizygotic and 34% (19/56) in monozygotic schizo+hrenic twin pairs. Luchins et al. (1980) are generally in agreement with Boklage since they report in the study of M Z twins with schizophrenia, that in twinships with at least one left-handed twin the sinistrals tend to suffer from a mild schizophrenia and the dextrals are not schizophrenic. These authors, pooling their own sample with that of Gottesman and Shields (1972) and of Pollin and Stabenau (1968) cumulate 20 1-2 L.H. twinships. 17 of the 23 (or 74%) of the sinistrals are schizophrenic as opposed to only 8 of the 17 (or 47%) dextrals. Thus concordance for schizophrenia is much higher in twin pairs where both are righthanded, but the probability of a schizophrenia type psychosis is greater in sinistrals. Contrary to Boklage when these authors examined the Gottesman and Shields sample for dizygotic twins a higher concordance for schizophrenia emerged in the 1-2 L.H.twinships than in the 2 R.H. pairs with 2 of 7 (or 28.6%) concordant for schizophrenia as contrasted to only 1 or 26 (or 3.8%) in the 2 R.H.pairs. This is the exact opposite of the situation found in monozygotic twins. The fact that in monozygotic twins discordant for schizophrenia and discordant for handedness, it is the sinistral member of the pair that is at risk for psychosis, at first glance appears to fit well with the with the CT scan investigations of twins discordant for schizophrenia undertaken by

Psychopathology

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Reveley et al. (1987) who found significantly lower left relative to right hemisphere density in the schizophrenic twin than in their healthy co-twin or in normal control twins. But, not in keeping with the pathological left-handedness hypothesis, in these 11 pairs of identical twins discordant for schizophrenia and 18 pairs of control twins, only one of the schizophrenics, none of their co-twins, and three of the control twins were left-handed. It should be noted that the frequently quoted notion that monozygotic twins are more likely to be lefthanded than the general population is not supported by a critical review of the evidence (McManus, 1980) which indicates that the incidence of sinistrality is the same in monozygotic, dizygotic or singletons. However, if a family history of sinistrality is present then the twins are discordant for handedness in 41% of instances, this falling to 16% in the absence of familial sinistrality. The figures cited are for monozygotic twins but the picture is similar for dizygotic pairs. Further Lewis et al. (1989) could not confirm in a recent English series the interactions described by Boklage. In this series of 44 psychotic twins 7 or 16% of the schizophrenics (ICD-9 criteria) were left-handed as opposed to 1 of 10 or 10% with other psychiatric diagnoses and 3 or 27 or 11% in normal twins. The criterion used was the hand preferred for writing. In their total sample of twins analyzed data was available for 125 subjects: 60 complete pairs, half monozygotic and half dizygotic. 14 of the 125 were left-handed. There was a trend towards higher rates in the schizophrenic subjects - however in the monozygotic pairs, discordant for psychosis, the proportion of left-handedness was similar in the discordant pairs (1 of 17 discordant) as opposed to 4 of 14 discordant in the twins concordant for schizophrenia. The authors point out that their failure to replicate Boklage, 1977 may be in part because of the criteria for hand preference. Their choice for definition of handedness is particularly unfortunate since with such a scheme the frequency of ambiguous handedness cannot be determined and it is largely in this area that there is an over representation of atypical handedness in schizophrenia. For example Satz et al. (1989) in the examination of 93 carefully diagnosed schizophrenics compared to 105 normal controls find 60% right-handed, 39% mixed and 2% left-handed in the patients as opposed to 82% right-handed, 14% mixed and 4% left-handed in the normal subjects. Satz et al. conclude that the excess of mixed-handedness in schizophrenia is robust (p<0.005). Lewis et al. (1989) in an important footnote report that in re-analysis of the Gottesman and Shields, (1972) series, at a 20year follow-up, less than half of the original probands fulfill RDC or DSM-I11 for schizophrenia. Retrospectively thus it would appear that the preponderance of

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sinistrals in the earlier series is brought about by schizo-affective or manicdepressive variants.

Sinistrality and Mood Moscovitch et al. (1981) documented excess dextrality (100%) in 52 patients with severe unipolar depressions requiring electroconvulsive therapy (ECT). Moreover, the incidence of familial sinistrality in first-degree relatives was only 5.7%, as opposed to 28.5% in the general population reviewed by Annett (1970) (p <0.01). In the study of bipolar psychoses, however, Sackeim and Decina (1983) encountered 29% sinistrality in the children of bipolar affective parents, as opposed to a 5% incidence in control children. The 113 parents had an incidence of sinistrality of 24.7%; this was even higher in bipolar I subjects (32.5% sinistral); bipolar I1 subjects showed 15.7% sinistrality. Similarly, Green et al. (1983), in the analysis of children born to schizophrenic parents, found 38% sinistrality,which contrasts with a 7.5% incidence in control children matched for age, sex and verbal IQ. Davidson and Schaffer (1983) confirmed earlier American studies that indicated that in the general population, independent of familial sinistrality, high anxiety subjects are significantly more sinistral than low anxiety groups. These authors measured anxiety in 538 college students, as a function of sex and handedness. Dextral females were significantly more anxious than dextral males and sinistrals were very significantly more anxious than dextrals. 4/7 (or 57%) of the subjects who were rated as most anxious were left-handed as opposed to 2/33 (or 6%) as least anxious (p cO.OoO6). Earlier Hicks and Pellegrini (1978) had obtained very similar results in 266 college students in whom handedness characteristics were correlated with scores on the Taylor Manifest Anxiety Scale. In the comparison of the 23 lefthanded and 12 mixed-handed subjects with the 35 students who were totally dextral the sinistral group scored significantly higher for anxiety than the purely dextrals. Orme (1970) measured emotional instability in 300 school girls from an approved school and contrasted the 23 (7.6%) who were left-handed with the 277 who were right-handed, both groups being of comparable and normal intelligence. Although the dextrals, here, were significantly more unstable than 143 control girls, the sinistrals were emotionally more unstable than the dextrals. Several authors in various countries have documented a curious interaction in which males with low monoamine oxidase activity were characterized by extraversion, impulsivity, ‘sensation-seeking’behaviours, suicidal attempts and

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dysphoric mood, i s . Von Knorring et al. (1984) in Sweden and Demisch et al. (1982) in Germany, (see Von Knorring et al. 1984 reference five other replications). Further Buchsbaum, (1977) showed that in the normal population sinistral males have significantly lower platelet MA0 activity whereas no male with high platelet MA0 activity was left-handed. In addition Von Knorring, (1984) found that in a large series of 1,129, 18 year old boys selected from the general population, low M A 0 activity subjects were very clearly left-handed. The table below shows how pronounced is the effect: Dextral

Low MA0 (30%) Normal or High MA0

x2

= 5.3,

S i n is t r a 1

290 (29.2%)

30 ( 4 2 . 2 % )

702 (94.5%)

4 1 (5.5%)

p < 0.02

von K n o r r i n g (personal comnunication, 1989)

Porac and Coren (1981) further discuss a number of studies undertaken in the 1920’s and 1930’s, all of which find evidence of increased sinistrality in emotionally disturbed children. It was noted above that Sackeim observed the unusually high incidence of 25% sinistrals in bipolar affective psychoses but that Moscovitch found 100% dextrality in severe unipolar depressions. Lishman and McMeekan (1976) found a slight but significant excess of sinistrality in 70 psychotics brought about principally by the manic-depressive and schizo-affective patients, i.e. bipolar states. Young psychotic males, irrespective of diagnosis were also more sinistral than expected by chance. Taylor et al. (1982) similarly reports that in both the Fleminger series and the Maudsley sample there is a trend whereby male schizophrenics are more sinistral and female schizophrenics more fully dextral. In a replication involving 114 consecutive schizophrenics and manic-depressives Flor-Henry and Yeudall (1979) found exactly the same increase in sinistrality in manic-depressive and schizo-affective psychoses as that reported by Lishman and McMeekan: 12% showed strong sinistrality largely because of an increase in inconsistent sinistrality (Annett, 1970) - i.e. twice the frequency found in the general population. That the excess in the bipolar psychoses should be of inconsistent, rather than consistent, sinistrality is of particular interest in the light of the report of H k a e n and Sauguet (1971) according to which the non-familial types of consistent sinistrality are similar to

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consistent dextrals in exhibiting an absence of language deficits after right brain lesions, while inconsistent sinistrals have bilateral language representation. In a series of papers I have argued the evidence that psychosis, the manifestation of altered bilaterally asymmetrical hemispheric organization, will necessarily be accompanied by alterations of lateral motor preference (FlorHenry, 1979a; 1983; Flor-Henry and Koles, 1980; Yan et al. 1985). The dextralitysinistrality dimension interacts in a complex manner with psychopathological expression and motor laterality and is a much more subtle indicator of unusual or altered hemispheric processes than is generally supposed. The description of a few single cases, admittedly exceptional, is illuminating. Lewis C. Bruce published in Brain in 1895 "notes of a case of dual brain action." This described a 47 year old Welsh sailor who suffered from a manic-depressive illness. When in the excited phase "talkative and mischievous" he was dextral and understood both Welsh and English. In the phase of melancholia he no longer understood English and became exclusively sinistral. During the transitions between depression and mania he was ambidextrous. When asked to write with his left hand during the manic phase (when he was dextral) he produced mirror writing from right to left. We have seen two related personal cases. The first was of a young man with unipolar depressive psychosis. When well he was ambidextrous; when depressed he lost the manual skill of his left hand, becoming completely dextrd, except for writing. Our second case was of a woman in her early fifties who proved to be 100% sinistral during a manic episode, becoming 100% dextral when asymptomatic. These last two examples suggest that depression, altering the organization of the right hemisphere, interferes with left hand dexterity and that mania, altering the organization of the left hemisphere, interferes with dextrality. The patient of Bruce shows the opposite: dextral when manic and sinistral when depressed, ambidextrous in the intervals. The picture here is further complicated by the fact that he was bilingual and it is now well established that the patterns of cerebral organization of bilinguals or polyglots is different to that of monolinguals. Notwithstanding, Corballis and Beale (1976) perhaps provide the clue: sinistrals or ambidextrous subjects capable of automatic mirror writing with the left hand are often right brain dominant, or have left hemisphere damage. In this context, it is also of relevance that 47% of patients with Multiple Personality shift handedness in the course of their transformations (Putnam et al., 1983). Since Lombroso (1903) associated criminality with left-handedness this issue has remained controversial. Hare and Forth (1985), commenting that research with adult criminals has produced inconsistent results, some showing an

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association of left-handedness with criminality, others failing to do so, find in a sample of 258 prison inmates no difference in hand preference distribution against a large normative sample of 1,211 control males. This was true for psychopathic and non-psychopathic criminals. If anything criminals were more right sided dominant than non-criminals. Porac and Coren (1981) however point out that in an earlier investigation (Hare, 1979) where the base rate of sinistrality in two criminal groups was similar to that seen in age-matched male controls (13.3% versus 11.4%) the non-psychopathic criminals have an incidence of lefthandedness of 8.3% whereas the psychopathic criminals with a frequency of 17.8% are significantly more left-handed. Wardell and Yeudall (1980) found that it was a sub-group of criminal psychopaths who were prone to sinistrality: those with a large verbal/performance IQ discrepancy (reduced verbal relative to performance abilities) and with psychopathy and schizophrenia elevations on the MMPI. Nachshon and Denno (1987) investigated the correlates of lateral preference and criminality, starting with a cohort of 2958 black children studied in Philadelphia in a perinatal project between 1959-1962. Selecting only males, with complete laterality data taken at age 7 and who were resident in Philadelphia up to the age of 18, a final sample of 1066 black males was obtained. Police records showed that 313 (or 29%) had been criminally charged and 10% violent. Unexpectedly, left-handedness was significantly more frequent in non-offenders than in offenders, there were no differences in foot or eye preference. Violent and non-violent offenders were similar for hand and foot preference but there was a significant difference for eye preference: 60% of the non-offenders and 64% of the non-violent offenders showed right eye preference whereas only 40% of the very violent offenders (n = 57, murder, rape, aggravated assault) were right eye preferent (p <0.008). 63% of the very violent and 60% of the violent offenders had cross preferences as opposed to 47% in all other groups. Citing evidence indicating that in males, birth stress is associated with left eye (but not left hand) preference and that visual evoked potentials are of higher amplitude from the dominant than the non-dominant eye and thus that there may be a hemisphere-eye association Nachshon and Denno conclude that their results suggest the presence of left hemisphere dysfunction in violent criminals, possibly the resuit of birth trauma. An important, and methodologically rigorous investigation on the association between sinistrality (left-handedness) and delinquency was published in 1980 by Gabrielli and Mednick. In this prospective study 265 children were intensively examined in 1972. They were extracted from the Danish peri-natal cohort of

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9,125 children consisting of all the children born between 1959 and 1961 at the Rigshospitalet in Copenhagen. All children with schizophrenic mothers or fathers (n = 72) were included and were matched against a group of children with psychopathic fathers, or character disordered mothers (n = 72). The remainder, 121 matched controls had parents free from psychiatric disorder. The delinquent individuals were identified from the Danish police register in 1978. Because, characteristically, only 7% of the girls were registered as delinquent they were discarded from the analysis. The final group, thus, consisted 36 boys with a schizophrenic parent, 36 with psychopathic father or character disordered mother and 57 with parents free from psychiatric disturbance. The offender group was considerably more sinistral, and this was independent of the presence or absence of mental illness in the parent. For instance 65% of the definitely left-handed boys were later arrested at least once but only 30% of the righthanded group. Low verbal IQ was correlated with criminality, but not with sinistrality. Neither neurological impairment nor social interaction factors (11 measures) correlated either with criminality or sinistrality. 33% of criminals with multiple arrests were sinistral; of those with a single crime 11% and in nonoffenders 7%. The evidence reviewed indicates that sinistrality is a modifying variable in a number of psychopathological syndromes. Given the fact that psychopathological syndromes are themselves heterogeneous, are not always similarly defined and that the methods of evaluating dextrality or sinistrality are often astonishingly dissimilar, there is no surprise that conflicting findings are frequent in this area of research. The majority of studies report an increased incidence of sinistrality in schizophrenia. Averaging the studies reviewed in this paper (Table 2) the incidence of sinistrality for the schizophrenics is 12%, i s . almost twice that of the combined controls (7%). There is a tendency for a male preponderance, early onset and progressive paranoid forms of psychosis with structural cerebral changes in this group. Some sub-populations of schizophrenics appear to exhibit excess dextrality. The available evidence suggests that these are the more acute schizophrenic syndromes, with florid, positive symptomatology, intermittent course and favourable outcome - as opposed to the chronic, deficit, negative symptomatologyschizophreniaswhere sinistralityis over-represented. Depending on the pathogenesis and its timing in development, intrauterine or post natal, the implications of a dextral of sinistral brain organization for schizophrenia will be different. Under certain circumstances subtle dysfunction in the left hemisphere will determine both a progressive schizophrenia and sinistrality. In &her

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circumstances, the more lateralized dextral brain will have less compensatory neural plasticity than the sinistral brain to a primary, or induced left hemisphere dysregulation. I suggested a few years ago (Flor-Henry, 1983) that the acute schizophrenias, with positive symptoms and frequent affective features are largely a variant of the affective psychoses but, in contrast to the purer manic-depressive bipolar psychoses that are associated with sinistrality, are more likely to exhibit first rank symptomatology through induced left hemisphere overactivation than the less lateralized classical bipolar syndrome. Even although not necessarily expressed through changed patterns of motor laterality there is evidence, both neurophysiological and neuropsychological, of altered left hemispheric functions during acute psychosis. Wexler and Heninger (1979) found in acute schizophrenia, acute mania and depression a temporary loss of right ear advantage to verbal dichotic stimuli during the psychotic episode. Hommes and Panhuyssen (1970) demonstrated by carotid barbiturization that dextral depressed patients no longer manifested aphasic responses after dominant hemisphere injections, this effect being significantly correlated with the intensity of the depression. Moreover the emotional reaction was euphoric, normally a feature of non-dominant hemisphere barbiturization. Mood regulation, recent evidence suggests, hinges on a complex reciprocity between the left and right frontal limbic zones, stability maintained by mutually interacting contralateral inhibition, with different emotions having different lateralization. The overall regulation of mood, however, appears to be the result of left frontal inhibitory regulation of right hemispheric systems. (Flor-Henry, 1979b, 1986). If this representation is, in its essential aspects, accurate then the interaction between mood instability and sinistrality immediately follows at the theoretical level. As we have seen the empirical evidence supports such an association, both in the general population, in a particular personality type and in the bipolar psychoses. A sub-population of criminal psychopaths, on the evidence to date, are clearly more sinistral than the general population. Only some express, through altered motor laterality, the subtle dysfunction of dominant hemispheric functions that is a fundamental aspect of the cerebral disorganization of the male psychopath (See Flor-Henry, in Press for review).

Conclusion The evidence reviewed shows that the incidence of certain psychiatric disorders is increased in sinistral populations. In a few others there appears to

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be an increase in full dextrality. These observations are theoretically important. The origins and consequences of sinistrality in schizophrenia are different in monozygotic twins, dizygotic twins and in singletons. The concordance for schizophrenia is much higher in R.H. - R.H. pairs than in 1-2 L.H. pairs monozygotic twinships but the reverse is true for dizygotic twins with a higher probability of illness in both twins when discordant for handedness. The severity of illness is most severe in RH-RH monozygotic when both are likely to be affected, but the frequency of schizophrenia is much higher in 1-2 LH pairs who exhibit a milder form of illness. Given the fact that the original diagnosis of schizophrenia in the original series could only be maintained in less than 50% of cases, it seems probable that these latter are largely manic-depressive or schizo-affectivevariant of the syndrome; which, in singletons are also associated with excess sinistrality. It cannot be overemphasized that being a twin is biologically extremely hazardous, both during intrauterine and post-natal life. Not only are general pregnancy complications such as toxaemia greater, but problems specific to twin pregnancy arise: foetal crowding, unequal distribution of blood supply, the so called ‘placental transfusion syndrome’ and shorter gestation, with lower birth weight. 55% of twin births are premature and a third of the deliveries are breech - as opposed to 3% in the general population. Low birth weight is a risk factor for schizophrenia in singletons and breech for autism. One in six of all multiple pregnancies in England terminate with the death of one or both twins (Dunn, 1965). Numerous studies over the last 50 years have shown that twins have a specific deficit in language abilities, corresponding to about 6 months developmental delay when compared to controls (reviewed by Mittler, 1971). Supporting Boklage, this can be viewed as the expression of disturbed symmetry fundamental to the twinning process: one twin is derived from a partially differentiated left and the other from a partially right differentiated half of a single embryo (Newman, Freeman and Holzinger, 1937). Why should sinistrality be a modifying variable associated with a mild illness in monozygotic twins, but with a severe illness in singletons? The origins of schizophrenia are multiple as are the determinants of sinistrality. Both schizophreniaand sinistrality are fundamentallyrelated to a functional alteration of dominant hemispheric systems. A sinistral pattern of brain organization may be the result of 1- genetic influences; 2- compensatory to left hemisphere damage, especially if sustained before the age of five years. In an important communication O’Callaghan et al. (1987) have drawn attention to a third mechanism: a failure in the development of normal right/left temporal neuroanatomical asymmetries which occurs around the 31 week of pregnancy.

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Studying at the age of four the handedness of extremely low birth weight infants, born at 26 and 29 weeks gestation and all weighing less than 1,OOO g, it was found that the handedness preference was random, with 54% sinistral. In children over 1,OOO g handedness was similar to control children (8% and 15% respectively). None of the very low birth weight children had cerebral palsy and they were of average intelligence. That their sinistrality was not the result of ‘pathological left-handedness’ was indicated by the absence of a gradation in frequency of left-handedness from the very low birth weights to the heavier infants. Pollin and Stabenau (1968) found, in 100 monozygotic twins discordant for schizophrenia that birth complications were four times more frequent in the schizophrenic than in the healthy co-twin. Chitkara et a]. (1988) compared the diagnostic distribution in 20,895 patients at the Maudsley Hospital with that of 504 patients born twins, including 117 twins (or 23%) where the co-twin had died before the age of 15. There was a significant excess of schizophrenia, personality disorders and substance abuse in the sub-group where the co-twin had died at birth or in early childhood: a subgroup which also had significantly more birth and perinatal complications and more males. When both twins survive - and one remains healthy, and only one monozygotic twin becomes schizophrenic, the hypodensity of the left hemisphere in the affected is not associated the sinistrality. The inference is that the pathogenic factors, if developmental, operated after 31 weeks of gestation, or if, as is more probable, of brain damage type, were sufficient to induce pathological changes in the left hemisphere, but not severe enough to induce pathological sinistrality. Hence, perhaps the reason for the more benign illness, in the left-handed subject in monozygotic pairs discordant for schizophrenia and discordant for handedness. In the right-handed monozygotic twins concordant for schizophrenia there is no birth trauma effect in evidence (Boklage, 1977). The pathogenic influences must therefore lie essentially in the consequences of the twinning process itself, leading to a more severe illness because of their greater lateralization. In this situation the sinistral twin would be protected from schizophrenia by the more bilateral pattern of brain organization - hence the high concordance for schizophrenia in dextral pairs with the malignant syndrome. Thus, the paradox that in monozygotic twins sinistrality protects against schizophrenia in the absence of external cerebral insult but if the latter is present increases the probability of schizophrenia. An accentuation of this process would produce increased sinistrality. The absence of sinistrality in this group is striking, if we recall that the incidence of sinistrality in monozygotic twins with a history of familial sinistrality is very high: 41% and that in the general population 30% - 35% have first degree relatives who are

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left-handed. Hence the very high concordance for schizophrenia since these subjects are identical, with the same ‘flaw’ in lateral symmetry organization; unmodified by external intrauterine or perinatal events. Dizygotic twins are essentially singletons sharing the same uterus, and therefore are especially at risk for acquired brain-damage during the latter part of gestation and early postnatal life. Should these adverse events occur, both twins would be exposed to the increased risk factors: hence the greater concordance for schizophrenia in dizygotic pairs with at least one left-handed member, and the greater risk for the sinistral: the pathological left-handedness effect. The brain-damage model also fits the general population of schizophrenics with severe manifestation of the illness: early onset males, with absence of family history for psychosis, and structural pathology specifically involving the left hemisphere (see for review Flor-Henry, 1989). In the absence of brain-damage the more lateralized dextral brain is more susceptible to induced dysfunction leading to acute schizophrenia, positive symptomatology with first rank symptoms, which have been correlated with left-lateralized changes in regional cerebral circulation (Uchino et al. 1987). Hence the excess dextrality in this group, and in the subgroup of chronic severe depressions. This sub-group, described by Moscovitch et al. (1981) consisted of unipolar depression, is 80% female and exhibits a striking absence of sinistrality, both in the patients and their first degree relatives. Modern evidence suggests that the left hemisphere, through contralateral inhibitory regulation, modulates emotional and aggression related neural subsystems in the right hemisphere. Given the relative vulnerability of the left hemisphere in males, the excess sinistrality seen in male psychopathy and in males with low MA0 activity and ‘sensation-seeking’behaviours is theoretically to be expected. Similarly the association of left-handedness with emotional instability, in both sexes, and with the bipolar psychoses immediately follows. Finally, it is perhaps worth observing that, in the sinistrality-psychopathology interactions discussed, the modifying influence of gender is clearly evident in the psychiatric categories discussed - but, except for the special case where the cotwin does not survive, it is absent in twins. This is another illustration of the exceptional and neurobiologically hazardous situation intrinsic to twinship and which overrides the more subtle, gender related, cerebral effects which can be manifested in singletons.

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