Personality measures in former heroin users receiving methadone or in protracted abstinence from opiates.

OBJECTIVE: Methadone Maintenance Therapy (MMT) and detoxification to abstinence are among the most common treatment options for opiate-dependent patients. This paper compares personality traits in detoxified former heroin users and those on MMT in order to assess their relevance to treatment selection. METHOD: Twenty-six formerly heroin-dependent subjects receiving MMT (MM), 33 formerly heroin-dependent subjects withdrawn from MMT (MW), and 43 healthy controls were compared on the Millon Clinical Multiaxial Inventory-II (MCMI-II) and the Temperament and Character Inventory (TCI). RESULTS: On the TCI, MM patients had higher novelty seeking and lower self-directedness scores than controls. Both MM and MW subjects scored higher than controls on multiple MCMI-II scales. MW but not MM subjects scored higher than controls on two Cluster A Scales and the delusional disorder scale. CONCLUSION: Schizophrenia-spectrum pathology in former opiate users may be greater than previously recognized and could potentially be relevant to treatment selection.

Cerebral metabolism in opiate-dependent subjects: effects of methadone maintenance.

BACKGROUND: The long-term effects of opiate use on human brain are not known. The goal of this preliminary study was to determine whether human subjects with histories of opiate dependence have persistent differences in brain function as compared with individuals without substance use disorders, and whether methadone maintenance reverses or ameliorates the potential abnormality. METHOD: Positron emission tomographic (PET) [18F]fluorodeoxyglucose (FDG) method was used to compare the regional cerebral metabolic rate for glucose(rCMRglc) in three groups: four opiate-dependent subjects currently receiving methadone maintenance therapy (MM), four opiate-dependent subjects not receiving methadone maintenance therapy (MW), and a comparison group of five subjects without substance use disorders. RESULTS: A significant difference in rCMRglc in the anterior cingulate gyrus was found between the MW and Control groups (Mann-Whitney U=2.0, p=0.05). Generally speaking, rCMRglc's in MM subjects were intermediate between those of MW and Control groups, although the difference did not reach statistical significance. CONCLUSIONS: The results of this study suggest that neurobiological abnormalities can persist in the brain of a chronic opiate user several years after detoxification from methadone. Future research is needed to replicate these results and to determine whether the observed rCMRglc differences are related to opiate use or to neurochemical abnormalities that play a role in developing addictive behavior.

Negative symptoms in patients with major depressive disorder: a preliminary report.

OBJECTIVE: The purpose of this study was to examine negative symptoms (NSs) in patients with major depressive disorder (MDD) and their relation to depressive symptoms (DSs) and other psychiatric symptoms. BACKGROUND: Features similar to NSs were previously described in patients with depression. METHOD: The Hamilton Rating Scale for Depression (HRSD), Positive and Negative Symptom Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), and Mini-Mental State Examination were administered to 23 patients with MDD and 10 normal control subjects. RESULTS: As expected, the mean scores of the HRSD, SANS, and negative symptom subscale of the PANSS of the patients with MDD were significantly higher than those of control subjects, validating the clinical significance of NSs as well as DSs in MDD patients. Within the MDD group, although measures of NSs were intercorrelated, there were no other correlations between the measures. Thus, measures of NSs and DSs were not intercorrelated. When the HRSD was divided in two subscales, HRSD negative symptom subscale scores but not HRSD depressive symptom subscale scores were correlated with PANSS negative symptom subscale and SANS total scores as well as with scores on the affective flattening subscale. CONCLUSIONS: These results suggest a high level of NSs in patients with MDD, which are distinct from positive symptoms of depression and may constitute a distinct dimension. Negative symptoms and DSs in MDD may represent separate constructs. Further, the HRSD might have possible subscales in MDD as it does in schizophrenia.

Psychiatric symptom severity and length of stay on an intensive rehabilitation unit.

The purpose of this study was to evaluate the role of psychiatric symptoms in the medical and surgical rehabilitation of patients on an intensive rehabilitation unit and to examine whether psychiatric symptom severity contributes to length of hospital stay (LOS). Forty-four patients (21 men and 23 women) were assessed at admission and before discharge with the Functional Independence Measure (FIM). Subjects were evaluated with the Mini-Mental State Exam (MMSE), the Hamilton Rating Scale for Depression (Ham-D), Positive and Negative Symptom Scale, (PANSS), and Scale for the Assessment of Negative Symptoms (SANS). Thirty-six percent of subjects were cognitively impaired (MMSE < 25), 14% had significant depressive symptoms (Ham-D > 12), and 52% had significant negative symptomatology (PANSS-N > 15). A regression analysis yielded a model of three predictive factors. Gender, the PANSS General subscale, and the SANS Attention subscale accounted for 42.4% of LOS variance. These results indicate that psychiatric symptoms are common in medical rehabilitation inpatients and, together with demographic factors, are associated with increased LOS.

Hypofrontality and negative symptoms in patients with dementia of Alzheimer type.

OBJECTIVE: The purpose of the current study was to examine the relation between regional cerebral blood flow (rCBF) and negative symptoms (NS) in patients with dementia of Alzheimer type (DAT). BACKGROUND: Negative symptoms in neuropsychiatric disorders were associated with altered rCBF in frontal cortex. METHODS: Twenty-five subjects with a diagnosis of DAT were administered the Scale for the Assessment of Negative Symptoms (SANS), the Positive and Negative Symptom Scale, the Hamilton Rating Scale for Depression, and the Mini-Mental State Examination. The subjects were divided into two groups by means of a median split with regard to NS severity (high NS group, N = 12; low NS group, N = 13). Each patient underwent a single photon emission tomography scan using 99mTc-HMPAO at rest. Cortical and subcortical regions of interest were symmetrically defined in each hemisphere. Cortical-to-cerebellar perfusion ratios were established quantitatively using ADAC software. RESULTS: High NS group subjects had a significantly lower rCBF than low NS group subjects in the frontal cortex and cingulate gyrus (MANOVA: p = 0.022) as a result of differences in the dorsolateral prefrontal cortex bilaterally (right: F = 12.12, p = 0.002; left: F = 6.55, p = 0.02) and in the frontal cortex, mainly in the right hemisphere (right: F = 6.33, p = 0.02; left: F = 3.26, p = 0.08). For all the subjects (N = 25), there were negative correlations between the SANS total score and rCBF, most prominently in the dorsolateral prefrontal cortex bilaterally (right: r = -0.48, p <0.01; left: r = -0.49, p = 0.01). No significant correlation was found between rCBF in any of the regions of interest and either the Mini-Mental State Examination or the Hamilton Rating Scale for Depression scores. CONCLUSIONS: This study indicates that decreased perfusion in the frontal cortex is associated with NS severity but not with measures of cognitive impairment or depressive symptoms in DAT patients. These results support the hypothesis that the frontal lobes may be involved in the cause of NS in DAT, and they underscore the importance of NS evaluation in neuroimaging studies.

Depression and demoralization among Russian-Jewish immigrants in primary care.

The purpose of this study was to examine the levels and nature of psychological distress and depression among Russian-Jewish émigrés in primary care. Fifty-seven consecutive patients at the primary care clinic were assessed with the Hamilton Depression Scale (Ham-D). The subjects completed self-rating scales, including the Beck Depression Inventory (BDI), Life Orientation Test, Beck Hopelessness Scale, Attributional Style Questionnaire, and Snaith-Hamilton Pleasure Scale. Data on demographics and physical complaints were collected and analyzed. Of the patients studied, 82.5% experienced psychological distress (BDI > or = 10), and 43.9% had clinically significant depressive symptoms (Ham-D > or = 17). BDI and Ham-D scores were significantly correlated with the number of psychosomatic complaints, hopelessness, lack of optimism, anhedonia, and dysfunctional attributional style. The distressed, but not depressed, patients had preservation of hedonic capacity. The authors found a high rate of depression based upon Ham-D scores among the Russian-Jewish émigrés in primary care. The authors suggest that this high rate is attributable to a culturally specific tendency to express distress in somatic terms. The nature of distress was phenomenologically similar to demoralization.

Hypofrontality and negative symptoms in major depressive disorder.

UNLABELLED: The purpose of the current study was to compare regional cerebral blood flow (rCBF) in patients with major depressive disorder (MDD) to that of healthy subjects and to examine the relationship between rCBF, depressive symptoms (DS) and negative symptoms (NS) in these patients. METHODS: Eleven psychiatric inpatients with diagnosed (MDD) and 15 normal control subjects were administered the scale for the assessment of negative symptoms (SANS) and the modified Hamilton rating scale for depression with items descriptive of NS excluded (HRSD-DS). Each patient underwent a SPECT scan using 99mTc-HMPAO at rest. Cortical and subcortical regions of interest (ROIs) were symmetrically defined in each hemisphere. Cortical-to-cerebellar perfusion ratios were established quantitatively using ADAC software. RESULTS: Subjects in the MDD group had significantly lower rCBF in the frontal cortex and cinglulate gyrus (MANOVA, p = 0.038) due to differences in dorsolateral prefrontal cortex bilaterally (right F = 7.69, p = 0.01; left F = 8.41, p = 0.01) in the right orbitofrontal cortex (F = 6.79, p = 0.02) and in the cingulate gyrus (F = 5.34, p = 0.03). The MDD group also had lower rCBF in the posterior cortical structures (MANOVA, p = 0.072), which was due to decreased perfusion in the right parietal cortex (F = 7.54, p = 0.01). There were negative correlations between the SANS total score and rCBF in both the left dorsolateral prefrontal cortex (Pearson's correlation coefficient r = .-67, p < 0.05) and the left anterior temporal cortex (r = -0.71, p < 0.01) in MDD patients. Additionally, there were positive correlations between HRSD scores and rCBF in the left anterior temporal (r = 0.71, p < 0.01), left dorsolateral prefrontal (r = 0.70, p < 0.01), right frontal (r = 0.82, p < 0.01) and right posterior temporal (r = 0.74, p < 0.01) cortices. Cerebral blood flow was not correlated with either mini-mental state examination scores or age. CONCLUSION: This preliminary study replicates the finding of hypofrontality in MDD and indicates that decreased perfusion is associated specifically with negative symptom severity. These results support the hypothesis that, in MDD, negative symptoms and symptoms of depression are distinct phenomena and underscore the importance of negative symptom evaluation in neuroimaging studies of MDD and other disorders.

Negative symptoms in stroke patients and length of hospital stay.

The purpose of this study was to assess whether the presence and severity of psychiatric symptoms in stroke patients correlate with their length of stay (LOS) in a rehabilitation unit, with special emphasis on the role of negative symptoms (NS). Twenty-three stroke patients, consecutively recruited from the inpatient rehabilitation unit, were evaluated on admission with the Mini-Mental State Examination (MMSE), the Positive and Negative Symptom Scale (PANSS), the Hamilton Depression Rating Scale (HDRS), the Scale for Assessment of Negative Symptoms (SANS), and the Functional Independent Measure (FIM). NS scores significantly correlated with LOS, with SANS total score being the most informative, and the attentional impairment subscale the least. The group of patients with pronounced NS stayed in the hospital twice as long as patients with the score on the NS subscale of PANSS below 16. These two groups did not differ in their cognitive performance or in the positive symptom subscale of PANSS scores. Total FIM score on admission was lower and HDRS scores higher in patients with pronounced NS. However, these differences, unlike those of LOS, have not reached statistical significance. The presence and severity of NS in stroke patients are associated with a longer hospital stay. Identification and treatment of NS might lead to a faster discharge from rehabilitation unit.

Methylphenidate treatment of negative symptoms in patients with dementia.

This pilot study evaluated response of negative symptoms (NS) to methylphenidate in patients with dementia and relationships between NS, depression, and cognitive deficits in these patients. Consecutively admitted patients with NS and dementia--12 with dementia of Alzheimer's type and 15 with vascular dementia--were rated on severity of NS (SANS and PANSS-N scales), depressive symptoms (Ham-D), and cognitive impairment (MMSE) before and after treatment with methylphenidate. NS decreased significantly, and cognitive scores increased. A decrease in depression scores was nonsignificant after all variance attributable to NS was removed. NS, depression, and cognitive scores were not significantly intercorrelated. Results were similar for Alzheimer's and vascular dementia patients. Negative symptoms in dementia patients appear responsive to methylphenidate treatment. This effect may underlie putative changes in symptoms of depression observed by other researchers.

ECT treatment and cerebral perfusion in Catatonia.

A 40-yr-old woman with a diagnosis of schizoaffective disorder developed catatonia in the context of a depressive episode. A dramatic decrease in perfusion of the inferior frontal, posterior temporal and parietal lobes bilaterally and in posterior frontal lobes corresponding to the motor cortices was noted on the 99mTc-HMPAO SPECT scan obtained in the acute phase. The most dramatic decreases compared to normal control subjects were observed in the left parietal and left motor cortices. The patient was treated with a five-treatment course of electroconvulsive therapy (ECT), which resulted in a complete resolution of catatonia and some resolution of her symptoms of depression. The repeat HMPAO-SPECT scan showed improved perfusion in all areas. The most dramatic increases occurred in the left parietal and left motor cortices. Decreased perfusion in motor and parietal cortices could be state-specific to catatonia. Thus, SPECT imaging may be a useful method for monitoring catatonia treatment response.

Panic attacks with psychotic features.

BACKGROUND: Anxiety disorders are among the most frequently diagnosed group of psychiatric disorders in the general population. Although anxiety disorders are often comorbid with depression and personality disorders, they rarely culminate in psychosis. METHOD: Having observed psychosis in the course of a severe panic attack, the authors prospectively identified four patients who experienced panic attacks with co-occurring psychosis. All met the DSM-IV criteria for panic disorder. Distinctive features of their clinical presentation, pharmacotherapy, and follow-up were recorded. RESULTS: Three patients had a history of panic disorder, and one had a history of generalized anxiety disorder. In all cases, psychosis (auditory hallucinations or delusions) originated in the course of a severe panic attack. Psychotic symptoms occurred only during panic attacks; however, these could occur up to 10 to 15 times a day. In all four patients, psychotic symptoms resolved after a brief time either spontaneously or with benzodiazepine/SSRI treatment. None of the patients required neuroleptic treatment. CONCLUSION: The cases suggest that psychosis may develop in the course of a severe panic attack in patients with panic disorder, as was reported previously for patients with obsessive-compulsive disorder and posttraumatic stress disorder. Distinguishing panic attacks with psychotic features from other psychotic disorders is clinically important since antipsychotic medication treatment for these psychotic symptoms is not indicated. Further research on the prevalence of psychotic symptoms in the anxiety disorders and the pathophysiology of this phenomenon is required to clarify the relationship between the anxiety disorders and psychosis.

Opioid receptor imaging and displacement studies with [6-O-[11C] methyl]buprenorphine in baboon brain.

Buprenorphine (BPN) is a mixed opiate agonist-antagonist used as an analgesic and in the treatment of opiate addiction. We have used [6-O-[11C]methyl]buprenorphine ([11C]BPN) to measure the regional distribution in baboon brain, the test-retest stability of repeated studies in the same animal, the displacement of the labeled drug by naloxone in vivo, and the tissue distribution in mice. The regional distribution of radioactivity in baboon brain determined with PET was striatum > thalamus > cingulate gyrus > frontal cortex > parietal cortex > occipital cortex > cerebellum. This distribution corresponded to opiate receptor density and to previously published data (37). The tracer uptake in adult female baboons showed no significant variation in serial scans in the same baboon with no intervention in the same scanning session. HPLC analysis of baboon plasma showed the presence of labeled metabolites with 92% +/- 2.2% and 43% +/- 14.4% of the intact tracer remaining at 5 and 30 min, respectively. Naloxone, an opiate receptor antagonist, administered 30-40 min after tracer injection at a dose of 1.0 mg/kg i.v., reduced [11C]BPN binding in thalamus, striatum, cingulate gyrus, and frontal cortex to values 0.25 to 0.60 of that with no intervention. There were minimal (< 15%) effects on cerebellum. Naloxone treatment significantly reduced the slope of the Patlak plot in receptor-containing regions. These results demonstrate that [11C]BPN can be displaced by naloxone in vivo, and they affirm the feasibility of using this tracer and displacement methodology for short-term kinetics studies with PET. Mouse tissue distribution data were used to estimate the radiation dosimetry to humans. The critical organ was the small intestine, with a radiation dose estimate to humans of 117 nrad/mCi.

Cognitive impairment in psychiatric patients and length of hospital stay.

The purpose of this study was to determine whether brief neuropsychologic screening at the time of admission to an acute-care psychiatric unit predicts the length of inpatient hospital stay (LOS). Over a 4-month period, 41 consecutively admitted patients on a general psychiatric inpatient unit were administered the Mini-Mental State Examination (MMSE), the Trails A and B subtests from the Halstead-Reitan Neuropsychological Battery, and the Visual Reproduction subtest (VR) of the Wechsler Memory Scale within 72 hours of admission. A setwise, hierarchic multiple regression model examined the contributions of demographic factors, clinical features, and the four neuropsychologic tests to LOS variance. VR and Trails A were the best predictors of LOS, responsible for 21.6% and 16.3% of outcome variance, respectively. The independent variables (IVs) comprising the best-fitting model include Trails A, VR, MMSE, and patient diagnosis. These variables collectively accounted for 48.8% of the variance in LOS, and predicted 70.4% of patients with LOS < 21 days and 82.4% of patients with LOS > 21 days. The results of this study support the hypothesis that LOS is related to cognitive impairment associated with psychiatric illness, and suggest that neuropsychologic testing upon admission to an inpatient unit can be useful in predicting LOS.

Methadone withdrawal psychosis.

BACKGROUND: Methadone is a typical mu-opioid receptor agonist that is widely used for maintenance and detoxification treatment of opiate-dependent patients. Although methadone withdrawal syndrome is well described, it generally does not include psychosis. METHOD: Having observed new onset psychosis in a patient on methadone taper, the authors identified three other such patients by chart review. All met DSM-III-R criteria for opioid dependence. Distinctive features of their clinical presentation, pharmacotherapy received, and follow-up were recorded. RESULTS: Two patients had no history of psychosis, one patient had a psychotic episode 21 years prior to admission, and one patient was diagnosed with schizophrenia but remained asymptomatic for at least 1 year while treated with only methadone. Psychosis resolved spontaneously in one case, whereas the other cases required neuroleptic treatment. In one case, methadone resumption was required. None of the patients developed typical methadone withdrawal syndrome. CONCLUSION: The above results suggest that opioid taper may be a period of high risk for development of psychosis. This risk is probably higher in patients with preexisting CNS illness. Clinicians caring for patients in opioid withdrawal should be aware of this risk. Further research is required to evaluate whether methadone withdrawal psychosis represents a clinical manifestation of opioid agonist modulation of dopaminergic neurotransmission in the human brain.