746
BIOL PSYCHIATRY 1992;31:746-748
Handedness as a Risk Factor for Neuroleptic-Induced Movement Disorders K. W° Brown, T. White, F. Anderson, and R. McGilp
DSM III-R criteria for chronic schizophrenia, have at least 5 years cumulative exposure to Tardive dyskinesia (TD) is one of the most seantipsychotic medication, be cooperative, and rious consequences of exposure to antipsychotic able to give verbal consent to assessment. A medication. Despite extensive research, there change in medication in the preceding month, remains disagreement over its etiology and risk muteness, established neurological disease, and factors. Likewise little is known about:tOe risk known intellectual impairment led to exclusion. factors for akathisia and drug-induced~parkinCurrent medication was converted to chlorsonism (DIP). promazine equivalents (Davis 1976). There is conflicting evidence on the role of Dyskinetic movements were assessed by the handedness as a risk factor. McCreadie et al Abnormal Involuntary Movements Scale (AIMS) (1982), in a survey of all schizophrenic inpa(NIMH 1976). TD was recorded as present in tients and outpatients in a discrete geographical those who satisfied the criteria of Schooler and area, found an excess of non-right-handedness Kane (1982) for persistent dyskinesia. (NRH) in dyskinetic, Feighner-positive subAkathisia was rated on a scale developed for jects. Joseph (1990) reported similar findings in this purpose (Brown et al 1987). In those sub48 consecutive outpatients with a variety of dijects without subjective symptoms of restlessagnoses. Ban" et al (1989), however, in a study ness evidence of particular patterns of objective on 43 inpatient schizophrenics, reported dexrestlessness which have been described as being trals to be at greater risk of developing TD. most discriminating tbr akathisia was required As the literature is inconclusive a further study (Braude et al 1983). is warranted. We have also sought to extend the Drag-induced parkinsonism was assessed on investigation to include akathisia and DIP. the ten-item scale of Simpson and Angus (1970). The cutoff score suggested by Simpson and AnMethod gus (1970) was adopted. All the movement disorder assessments were Forty-eight residents of several long-term wards undertaken by KWB and TW, blind to handat Leverndale Hospital, Glasgow were reedness. The hondedness rating were performed cruited, For inclusion the patients had to satisfy by FA and RM. The ratings were undertaken contemporaneously by a pair of raters and a final From Royal Edinburgh Hospital, 151 Momingside Place, Edin- score agreed. burgh, UK (KWB}, Parkhead Hospital, [03 Salamanca Street, Handedness was assessed using the EdinGlasgow, G31, UK (TW). and Leverndal¢ ii~pi|al, Crookston Road, Glasgow, UK (RML burgh Inventory (Oldfield 1971). This includes Address reprint requests to Dr, T. White, Parkhead Hospital, 103 ten questions on handedness and one each on Salamanca Streel. Glasgow 63 l, UK. Received May 28, 1991: revised October 3, 1991. the use of feet and eyes. As in the Joseph study
Introduction
© 1992 Society of Biological Psychiatry
0006-3223/92/$05.00
Brief Reports
toOLPSYCHIATRY 1992;31:746-748
Table 1. Demographic Data (n = 48) Mean (SD) Age (yr) Duration of medication (yr) Duration of illness (yr) Age of onset Current drugs in daily CPZ equivalents Sex (M:F) Presence Of anticholinergics
58.3 (7.9) 27. ! (7.4) 28.7 (10. I) 27.9 (7.9) 518 (588) 20:28 24/48
(I 990), only those questions related to hand use were utilized to quantify handedness. The summed scores for left.hand use were subtracted from those for right-hand use, giving a iaterality score (LS). Pure right-handedness received a LS of + 20. Any score less than this, thereby indicating some preferred use of the left hand, was referred to as non-right-handedness (NRH). This assignment of laterality was undertaken to facilitate comparison with the study of Joseph (1990).
Results The demographic details of sample are shown in Table I. No significant differences were found between those with and without TD, akathisia, and DIP. There was a trend though for the nondyskinetics to have an excess of females (F:M 6:1 versus 26:15). There was a significant difference in NRH between subjects with (0/21) and without TD (7/20) (p = 0.021, Fisher's exact test). No differences in NRH was found in those with and without akathisia (4/20 versus 3/20) and DIP (2/13 versus 5/28). As both age and ~ex may have some influence on handedness in schizophrenic subjects (Fleminger et al 1977; Taylor et al 1980), the association among these variables, handedness, and dyskinetic status was assessed using loglinear analysis. The age variable was dichotomized around an age of 55 years. This revealed a significant interaction between dyskinetic status and handedness (Marginal association X2 =
747
7.24, df= 1, p -- 0.007). When all the other two-way interactions are included this association remains significant (partial association )~2 = 6.61, df = 1, p = 0.01). Using a hierarchical model-fitting approach, the model that included the dyskinetic status and handedness gave the best measure of fit (X2 goodness of fit = 9.66, df = 12~ p ~- 0.645.)
r~;ocdssion We have found that dextrals are at greater risk of developing persistent TD, and that this survived correction for the potentially confounding variables of age and sex. No differences in handedness was found between those with and without akathisia and DIP. There are several methodological problems with this study that need to be addressed. The sample size was not large, although it was not materially different than those of Barr et al (1989) and Joseph (1990). The movement disorders were assessed blind to handedness, but the reverse may not have been the case due to the overt nature of the dyskinetic movements. Although seemingly straightforward, the assessment of handedness may pose many practical difficulties. Handedness may vary depending on whether it based on verbal reports or objective assessment. It may also vary with the motor task chosen. The patient sample may b~.unrepresentative in view of the severity and chronicity of their schizophrenic illness. There may be methodological differences that explain the discrepancy between our findings, and those of Barr et al (1989), and those reported by McCreadie et al (1982) and Joseph (1990). The patient samples are heterogeneous with regard to psychiatric diagnosis, thereby introducing possible cc.~lfounding variables. Different assessment and criteria for TD, schizophrenia, and handedness have been used. In our study all the subjects satisfied Schooler and Kane's criteria for persistent TD, which may be etiologically different from transient uyskinesias associated with recent change in drag dosage. It is unclear why handedness should serve as a risk factor for TD but not akathisia or DIP. It
748
BIOL PSYCHIATRY 1992;31:746-748
,/ /
,/ may be that treatment variables such as recent changes in medication are more important than patient variables in their development. However, our subjects were required to have had stable antipsychotic medication over the preceding month, and in many cases it had remained unchanged for a much longer period. It is interesting that both studies (Ours and that of barr et al 1989) based solely on inpatients reported an excess of dextrality in the dyskinetic subjects. This may be in keeping with Taylor's (1980) finding that pure dextrality was associated with a poorer outcome in schizophrenic subjects. This view is not undisputed. (Gur 197"/). In conclusion, our study lends weight to the conclusion of Barr et al (1989) that de×trals are more likely to develop TD. We found no evidence that handedness serves as a risk factor for akathisia or DIP.
References Annett M (1970): A classification of hand preferences by association analysis, Br J Psychiatry 61:303321. Ban WB, Mukherjec S, lkgreefG, Garacci G. (1989): Anomalous dominance and persistent tardive dyskinesit~. Bioi Psychiatry 25:826-834. Braude WM, Barnes ]'RE, Gore SM (1983): Clinical characteristics of akathisia: A systematic investigation of acute psychiatric inpatient admissions. Br J P~ychia;ry 143:139-150.
Brief Reports
/
Brown K W ~ l e n SE, White T 0987): Low serum iron ~ u s and akathisia. Lancet ii: 1234-1236. Davis JM (1976): Comparative dose and cost of antipsychotic medication. Arch Gen Psychiatry 33:858-861. Fleminger JJ, Dalton R, Standage KF (1977): Handedness in Psychiatric Patients. Br J Psychiatry 131:448-452. Gur RE (1977): Motor laterality imbalance in schizophrenia. Arch Gen Psychiatry 34:33-34. Joseph AB (1990): Non-right-handedness and maleness correlate with tardive dyskinesia among patients taking neuroleptics. Acta Psychiatr Scand 81:530-533. McCreadic RG, Crone J, Barron ET, Winslow GS (1982): The Nithsdale Schizophrenia Study: 111 handedness and t',u'divedyskinesia. Br J Psychia. try 140:591-594, National Institute of Mental Health (1976): Abnormal involuntary movement scale. In Guy W (ed), Early Clinical Drug Evaluation Unit Assessment Manual. Rockville, MD: US Department of Health and Human Services. Oldfield BC (1971): The assessment and analysis of the Edinburgh Inventory. Neuropsychologica 9:97!13. Schooler NR, Kane JM (1982): Research diagnosis of tardive dyskinesia. Arch Gen Psychiato, 39:686687. Simpson GM, Angus JWS (1970): A rating ,~cale for extra-pyramidal side-effects. Acta Psychiatr Scand 212(Suppl I):l 1-19. Taylor PJ, Dalton R, Fleminger JJ (1980): Handedhess in schizophrenia. Br J Psychiatry 136:375383.
BIOL PSYCHIATRY 1992;31:746-748
Handedness as a Risk Factor for Neuroleptic-Induced Movement Disorders K. W° Brown, T. White, F. Anderson, and R. McGilp
DSM III-R criteria for chronic schizophrenia, have at least 5 years cumulative exposure to Tardive dyskinesia (TD) is one of the most seantipsychotic medication, be cooperative, and rious consequences of exposure to antipsychotic able to give verbal consent to assessment. A medication. Despite extensive research, there change in medication in the preceding month, remains disagreement over its etiology and risk muteness, established neurological disease, and factors. Likewise little is known about:tOe risk known intellectual impairment led to exclusion. factors for akathisia and drug-induced~parkinCurrent medication was converted to chlorsonism (DIP). promazine equivalents (Davis 1976). There is conflicting evidence on the role of Dyskinetic movements were assessed by the handedness as a risk factor. McCreadie et al Abnormal Involuntary Movements Scale (AIMS) (1982), in a survey of all schizophrenic inpa(NIMH 1976). TD was recorded as present in tients and outpatients in a discrete geographical those who satisfied the criteria of Schooler and area, found an excess of non-right-handedness Kane (1982) for persistent dyskinesia. (NRH) in dyskinetic, Feighner-positive subAkathisia was rated on a scale developed for jects. Joseph (1990) reported similar findings in this purpose (Brown et al 1987). In those sub48 consecutive outpatients with a variety of dijects without subjective symptoms of restlessagnoses. Ban" et al (1989), however, in a study ness evidence of particular patterns of objective on 43 inpatient schizophrenics, reported dexrestlessness which have been described as being trals to be at greater risk of developing TD. most discriminating tbr akathisia was required As the literature is inconclusive a further study (Braude et al 1983). is warranted. We have also sought to extend the Drag-induced parkinsonism was assessed on investigation to include akathisia and DIP. the ten-item scale of Simpson and Angus (1970). The cutoff score suggested by Simpson and AnMethod gus (1970) was adopted. All the movement disorder assessments were Forty-eight residents of several long-term wards undertaken by KWB and TW, blind to handat Leverndale Hospital, Glasgow were reedness. The hondedness rating were performed cruited, For inclusion the patients had to satisfy by FA and RM. The ratings were undertaken contemporaneously by a pair of raters and a final From Royal Edinburgh Hospital, 151 Momingside Place, Edin- score agreed. burgh, UK (KWB}, Parkhead Hospital, [03 Salamanca Street, Handedness was assessed using the EdinGlasgow, G31, UK (TW). and Leverndal¢ ii~pi|al, Crookston Road, Glasgow, UK (RML burgh Inventory (Oldfield 1971). This includes Address reprint requests to Dr, T. White, Parkhead Hospital, 103 ten questions on handedness and one each on Salamanca Streel. Glasgow 63 l, UK. Received May 28, 1991: revised October 3, 1991. the use of feet and eyes. As in the Joseph study
Introduction
© 1992 Society of Biological Psychiatry
0006-3223/92/$05.00
Brief Reports
toOLPSYCHIATRY 1992;31:746-748
Table 1. Demographic Data (n = 48) Mean (SD) Age (yr) Duration of medication (yr) Duration of illness (yr) Age of onset Current drugs in daily CPZ equivalents Sex (M:F) Presence Of anticholinergics
58.3 (7.9) 27. ! (7.4) 28.7 (10. I) 27.9 (7.9) 518 (588) 20:28 24/48
(I 990), only those questions related to hand use were utilized to quantify handedness. The summed scores for left.hand use were subtracted from those for right-hand use, giving a iaterality score (LS). Pure right-handedness received a LS of + 20. Any score less than this, thereby indicating some preferred use of the left hand, was referred to as non-right-handedness (NRH). This assignment of laterality was undertaken to facilitate comparison with the study of Joseph (1990).
Results The demographic details of sample are shown in Table I. No significant differences were found between those with and without TD, akathisia, and DIP. There was a trend though for the nondyskinetics to have an excess of females (F:M 6:1 versus 26:15). There was a significant difference in NRH between subjects with (0/21) and without TD (7/20) (p = 0.021, Fisher's exact test). No differences in NRH was found in those with and without akathisia (4/20 versus 3/20) and DIP (2/13 versus 5/28). As both age and ~ex may have some influence on handedness in schizophrenic subjects (Fleminger et al 1977; Taylor et al 1980), the association among these variables, handedness, and dyskinetic status was assessed using loglinear analysis. The age variable was dichotomized around an age of 55 years. This revealed a significant interaction between dyskinetic status and handedness (Marginal association X2 =
747
7.24, df= 1, p -- 0.007). When all the other two-way interactions are included this association remains significant (partial association )~2 = 6.61, df = 1, p = 0.01). Using a hierarchical model-fitting approach, the model that included the dyskinetic status and handedness gave the best measure of fit (X2 goodness of fit = 9.66, df = 12~ p ~- 0.645.)
r~;ocdssion We have found that dextrals are at greater risk of developing persistent TD, and that this survived correction for the potentially confounding variables of age and sex. No differences in handedness was found between those with and without akathisia and DIP. There are several methodological problems with this study that need to be addressed. The sample size was not large, although it was not materially different than those of Barr et al (1989) and Joseph (1990). The movement disorders were assessed blind to handedness, but the reverse may not have been the case due to the overt nature of the dyskinetic movements. Although seemingly straightforward, the assessment of handedness may pose many practical difficulties. Handedness may vary depending on whether it based on verbal reports or objective assessment. It may also vary with the motor task chosen. The patient sample may b~.unrepresentative in view of the severity and chronicity of their schizophrenic illness. There may be methodological differences that explain the discrepancy between our findings, and those of Barr et al (1989), and those reported by McCreadie et al (1982) and Joseph (1990). The patient samples are heterogeneous with regard to psychiatric diagnosis, thereby introducing possible cc.~lfounding variables. Different assessment and criteria for TD, schizophrenia, and handedness have been used. In our study all the subjects satisfied Schooler and Kane's criteria for persistent TD, which may be etiologically different from transient uyskinesias associated with recent change in drag dosage. It is unclear why handedness should serve as a risk factor for TD but not akathisia or DIP. It
748
BIOL PSYCHIATRY 1992;31:746-748
,/ /
,/ may be that treatment variables such as recent changes in medication are more important than patient variables in their development. However, our subjects were required to have had stable antipsychotic medication over the preceding month, and in many cases it had remained unchanged for a much longer period. It is interesting that both studies (Ours and that of barr et al 1989) based solely on inpatients reported an excess of dextrality in the dyskinetic subjects. This may be in keeping with Taylor's (1980) finding that pure dextrality was associated with a poorer outcome in schizophrenic subjects. This view is not undisputed. (Gur 197"/). In conclusion, our study lends weight to the conclusion of Barr et al (1989) that de×trals are more likely to develop TD. We found no evidence that handedness serves as a risk factor for akathisia or DIP.
References Annett M (1970): A classification of hand preferences by association analysis, Br J Psychiatry 61:303321. Ban WB, Mukherjec S, lkgreefG, Garacci G. (1989): Anomalous dominance and persistent tardive dyskinesit~. Bioi Psychiatry 25:826-834. Braude WM, Barnes ]'RE, Gore SM (1983): Clinical characteristics of akathisia: A systematic investigation of acute psychiatric inpatient admissions. Br J P~ychia;ry 143:139-150.
Brief Reports
/
Brown K W ~ l e n SE, White T 0987): Low serum iron ~ u s and akathisia. Lancet ii: 1234-1236. Davis JM (1976): Comparative dose and cost of antipsychotic medication. Arch Gen Psychiatry 33:858-861. Fleminger JJ, Dalton R, Standage KF (1977): Handedness in Psychiatric Patients. Br J Psychiatry 131:448-452. Gur RE (1977): Motor laterality imbalance in schizophrenia. Arch Gen Psychiatry 34:33-34. Joseph AB (1990): Non-right-handedness and maleness correlate with tardive dyskinesia among patients taking neuroleptics. Acta Psychiatr Scand 81:530-533. McCreadic RG, Crone J, Barron ET, Winslow GS (1982): The Nithsdale Schizophrenia Study: 111 handedness and t',u'divedyskinesia. Br J Psychia. try 140:591-594, National Institute of Mental Health (1976): Abnormal involuntary movement scale. In Guy W (ed), Early Clinical Drug Evaluation Unit Assessment Manual. Rockville, MD: US Department of Health and Human Services. Oldfield BC (1971): The assessment and analysis of the Edinburgh Inventory. Neuropsychologica 9:97!13. Schooler NR, Kane JM (1982): Research diagnosis of tardive dyskinesia. Arch Gen Psychiato, 39:686687. Simpson GM, Angus JWS (1970): A rating ,~cale for extra-pyramidal side-effects. Acta Psychiatr Scand 212(Suppl I):l 1-19. Taylor PJ, Dalton R, Fleminger JJ (1980): Handedhess in schizophrenia. Br J Psychiatry 136:375383.
