Relapse of paranoid psychotic state in methamphetamine model of schizophrenia.

The study of the clinical course of methamphetamine (MAP) psychosis yields insights into the biological aspect of the relapse of the paranoid psychotic state with hallucination in schizophrenia. A series of MAP psychosis studies in Japan conducted over a period of more than four decades revealed three types of clinical courses of MAP psychosis after discontinuation of MAP: transient type, prolonged type, and persistent type. Identification of the latter two indicates a lasting change in the brain that produces and maintains a schizophrenia-like paranoid psychotic state without MAP. The characteristic course seen in the transient type is acute recurrence of the psychotic state after a long remission period, almost identical to the initial episode, due to reuse of MAP or to psychological stressors. Such lasting vulnerability of the brain to schizophrenia-like psychotic symptoms may be caused by a lasting sensitization of the brain to the psychotogenic action of MAP resulting from its chronic abuse. Experimental studies using animals sensitized to MAP-induced stereotypy suggest that lasting enhancement of MAP-induced dopamine release in the striatum and nucleus accumbens is related to the development and expression of brain vulnerability to schizophrenic symptoms.     

Clinical features of recent methamphetamine abusers: comparison between smoking abusers and injection abusers]

The author studied the clinical features of recent methamphetamine (MAP) abusers in Japan by comparing two methods of MAP use: smoking and injection. Of all the methamphetamine abusers that consulted Kanagawa Prefectural Center of Psychiatry, Serigaya Hospital, between June '97 and November '98, 67 patients that the author interviewed and treated were selected to participate in this study. The subjects consisted of two groups: 31 smoking abusers and 36 injection abusers. The results clearly showed the following: 1. Injection abusers tended to abuse organic solvents in addition to MAP, and had criminal records, lower education, and alcoholic parents more often than smoking abusers. On the other hand, smoking abusers tended to abuse cannabis, and lived in an environment similar to the general population. 2. Smoking abusers could not control MAP use, and developed acute psychotic symptoms such as hallucinations and delusions more quickly than injection abusers. 3. No remarkable differences in psychotic symptoms at acute intoxication among the two groups were seen; however, injection abusers showed more auditory hallucinations at first consultation. 4. No remarkable differences in the percentage of prolonged/chronic psychosis were detected among the two groups; however, injection abusers with psychosis needed higher doses of neuroleptics. 5. The families of smoking abusers attended family seminars more than those of injection abusers; however, there were no remarkable differences in the prognosis of the addiction rehabilitation program between the two groups. Based on the results, the author proposed a new type of MAP abuser was generated when smokable MAP was introduced to Japan. Furthermore, it was found that smokable MAP is more likely to cause loss of control and acute psychosis. However, this speculation was solely based on observation and treatment of abusers who sought consultation at medical facilities, and numerous smoking abusers who have not received treatment are considered to exist.     

Determining vulnerability to schizophrenia in methamphetamine psychosis using exploratory eye movements

Patients with methamphetamine (MAP) psychosis whose psychotic symptoms continued after MAP withdrawal were observed at Saitama Prefecture Government Psychiatric Hospital. The purpose of the present study was to ascertain whether some of these MAP psychosis subjects have a vulnerability to schizophrenia. Forty-eight patients with MAP psychosis were divided into three groups based on clinical course: transient type, prolonged type and persistent type. Furthermore, the patients with the persistent type were divided into two groups: one group were moderately disturbed in social adaptive functioning and had Global Assessment Functioning scale (GAF) points >50, and the other group consisted of those who were severely disturbed in social adaptive functioning and who had GAF points of < or =50. These MAP patients were tested for exploratory eye movements, which are the vulnerability marker of schizophrenia, and were compared with 30 patients with schizophrenia and 30 healthy control subjects. The responsive search score of the severely disturbed group of patients of the persistent type was lowest, significantly lower than those of the transient type and the healthy controls. It did not differ from that of the schizophrenic subjects. These results suggest that the severely disturbed group of patients with the persistent type of MAP psychosis have a vulnerability to schizophrenia.     

Predictors of methamphetamine psychosis: History of ADHD-relevant childhood behaviors and drug exposure

The goal of this study was to extend our previous research that reported a significant association between Attention Deficit Hyperactivity Disorder (ADHD)-relevant childhood behaviors and the frequency of methamphetamine (MA)-induced psychotic symptoms in an expanded sample. 190 participants who met DSM-IV criteria for MA dependence were administered the Methamphetamine Experience Questionnaire that assessed MA-induced psychosis. Data related to MA exposure, comorbid drug use, education, familial psychiatric history and assessments of ADHD-relevant childhood behaviors as measured by the Wender Utah Rating Scale (WURS) were collected. Although WURS scores did not differ between 145 MAP+ and 45 MAP- subjects, MAP+ subjects with higher WURS scores were significantly more likely to report more frequent psychosis. Although mean daily MA dosage did not differ between the MAP+ and MAP- subjects, MAP+ subjects who consumed larger doses of MA were significantly more likely to experience frequent psychosis. These data suggest that ADHD-relevant childhood behaviors may interact with MA exposure to reflect a neurobiological vulnerability related to the emergence of frequent MA-induced psychotic symptoms. These results may elucidate factors that contribute to the psychiatric sequelae of MA abuse.     

Chronic methamphetamine intoxication model of schizophrenia in animals.

The chronic methamphetamine (MAP) intoxication model of schizophrenia in animals is outlined. The idea originated from the clinical and neurochemical similarities between MAP psychosis and schizophrenia that were found during the decade immediately after World War II when MAP abuse occurred in epidemic proportions in Japan. The chronic intoxication model is produced by daily injections of a small dose of MAP into animals for several weeks or months. Behavioral studies with various species of animals from guinea pigs to monkeys produced essentially the same disorders as those observed in human abusers. Specifically, monkeys manifest psychotic behaviors, which appear to result from perceptual-cognitive disturbances, as well as enduring autistic behavior disorders that resemble the defect symptoms in chronic schizophrenia. Furthermore, the psychotic behaviors were found to have a high relapse liability; they recurred readily after the readministration of the drug or under nonspecific stress conditions. The difference and relationship between the chronic MAP intoxication model and the amphetamine stereotypy (acute intoxication) model are discussed.     

Diagnosing psychotic disorders in the emergency department in the context of substance use

OBJECTIVE: For patients who are actively using a substance and experience psychotic symptoms, determining whether the psychotic symptoms are due to a primary psychotic disorder or are substance induced is challenging, especially in emergency departments, where historical information is limited. This study examined the accuracy and subsequent treatment implications of emergency department diagnoses among substance-using patients who were having their first psychotic episode. METHODS: Emergency department diagnoses for 302 patients were compared with best-estimate longitudinal diagnoses (BELDs) based on research assessments at three time points (baseline, six months, and 12 months). RESULTS: Of the 223 patients whose symptoms were diagnosed in the emergency department as a primary psychotic disorder, one-quarter were determined by the BELD to have substance-induced psychosis or no psychosis. Overall, the diagnostic agreement was only fair (kappa=.32). Patients with an emergency department diagnosis of primary psychosis were significantly more likely than those with an emergency department diagnosis of substance-induced psychosis to be hospitalized, started on antipsychotic medication, and referred to mental health services instead of treatment for substance use (p<.001). Patients given an emergency department diagnosis of primary psychosis who were found by the BELD to have substance-induced psychosis or no psychosis were significantly more likely to be treated for a psychotic disorder rather than for substance-induced psychosis (p<.001) CONCLUSIONS: Clinicians in psychiatric emergency departments appear to have a tendency to attribute psychotic symptoms to a primary psychotic disorder rather than to concurrent substance use. Given that the diagnosis has significant implications for future management, it is important to improve diagnostic approaches in the emergency department.     

Correlates of psychotic symptoms among elderly outpatients.

Psychotic symptoms presenting in late life can offer a diagnostic challenge to the clinician. In this study, 140 geriatric outpatients were prospectively examined for psychotic symptoms and assessed on a number of demographic and clinical variables. Cognition was assessed using the Mini-Mental State Exam. Psychiatric diagnoses were made by DSM-III-R criteria. Twenty-seven per cent (N = 38) had psychotic symptoms, delusions being the most common type. Patients with psychosis were significantly more likely to have a previous history of psychosis, to have a lower MMSE and to live in a nursing home. Four diagnoses accounted for 79.5% of all psychotic patients. In order of frequency, these were dementia, major depression, delirium and organic psychosis (organic hallucinosis, organic delusional disorder). Psychotic patients were significantly more likely to have a diagnosis of dementia, delirium or organic psychosis than non-psychotics, but depression was significantly more likely to occur in patients without psychosis. Although psychotic symptoms occur in a variety of illnesses, elderly patients with psychosis should be carefully evaluated for these disorders.     

Chronic Schizophrenia-Like States in Methamphetamine Psychosis

Abstract: In order to clarify the characteristic psychopathology of chronic methamphetamine (MAP) psychosis, the clinical symptoms of 11 chronic MAP psychotics were compared with those of the same number of chronic schizophrenics matched for sex and age. The positive symptoms were almost similar in both groups. However, the negative symptoms evaluated by the Scale for the Assessment of Negative Symptoms (SANS) differed considerably. According to the SANS, the scores of avolition-apathy, anhedonia-asociality and attentional impairment were moderately high in both groups. The scores of affective flattening or blunting and alogia were lower in the MAP group than those in the schizophrenia group. The SANS scores of negative symptoms increased in accordance with the age of onset in the MAP group, while such a correlation was not observed in the schizophrenia group. Furthermore, detailed clinical observations of the patients revealed the following differences between the two groups: 1) spontaneous affective expression during the interviews was more vivid in the MAP group compared to the schizophrenia group, and 2) affective expressions or interpersonal behaviors changed immediately depending on the situation in the MAP group. From the viewpoint of clinical psychopathology, a group of MAP psychotics whose hallucinatory-delusional state persisted for a long period of one month or more after cessation of MAP use seemed to differ from either chronic schizophrenics or patients with acute MAP psychosis. The author proposed that this group of patients should be a clinical entity and be called as "residual methamphetamine psychosis."     

Chronic schizophrenia-like states in methamphetamine psychosis

In order to clarify the characteristic psychopathology of chronic methamphetamine (MAP) psychosis, the clinical symptoms of 11 chronic MAP psychotics were compared with those of the same number of chronic schizophrenics matched for sex and age. The positive symptoms were almost similar in both groups. However, the negative symptoms evaluated by the Scale for the Assessment of Negative Symptoms (SANS) differed considerably. According to the SANS, the scores of avolition-apathy, anhedonia-asociality and attentional impairment were moderately high in both groups. The scores of affective flattening or blunting and alogia were lower in the MAP group than those in the schizophrenia group. The SANS scores of negative symptoms increased in accordance with the age of onset in the MAP group, while such a correlation was not observed in the schizophrenia group. Furthermore, detailed clinical observations of the patients revealed the following differences between the two groups: 1) spontaneous affective expression during the interviews was more vivid in the MAP group compared to the schizophrenia group, and 2) affective expressions or interpersonal behaviors changed immediately depending on the situation in the MAP group. From the viewpoint of clinical psychopathology, a group of MAP psychotics whose hallucinatory-delusional state persisted for a long period of one month or more after cessation of MAP use seemed to differ from either chronic schizophrenics or patients with acute MAP psychosis. The author proposed that this group of patients should be a clinical entity and be called as "residual methamphetamine psychosis."     

Increased number of offspring in first degree relatives of psychotic individuals: a partial explanation for the persistence of psychotic illnesses

Objective: As patients with psychotic illness have fewer offspring than controls, the persistence of psychotic illness is puzzling. We hypothesized that unaffected first‐degree relatives of patients have more offspring than controls. Method: Probands were 4904, individuals with non‐affective psychotic disorders identified from a hospitalization registry. Unaffected first degree relatives and matched controls were identified from the Israeli Population Registry. The number of offspring of unaffected parents, biological siblings and controls was ascertained. Results: Unaffected parents of psychotic patients had more offspring/person than controls; 4.5 ± 2.7 vs. 3.4 ± 2.2, P = 0.000. Unaffected parents from familial psychosis families (more than one affected family member) had 1.83 more offspring than controls; unaffected parents from non‐familial psychosis families had 0.97 more offspring than controls (both P < 0.001). Conclusion: These findings might imply that genes which increase susceptibility for schizophrenia may be associated with increased number of offspring, perhaps supplying a partial explanation for the persistence of psychosis.     

Les psychoses postictales

In epilepsy patients, psychotic states are related to a group of psychotic disorders with a specific phenomenology in which potential pathophysiological mechanisms are believed to be closely related to the epileptic disorder itself. Postictal psychosis is a very specific syndrome in relation to seizure activity: a clear temporal relationship exists between the psychotic state of sudden onset and a precipitating bout of complex partial or generalized seizures, with a characteristic lucid interval which lasts from two to 120 h. The psychotic state may be related to the withdrawal of anticonvulsants, often in connection with video-EEG monitoring. The phenomenology of the psychotic state is often pleomorphic, with abnormal mood, paranoid delusions and hallucinations, with some clouding of consciousness or no evidence of impaired consciousness. The outcome is characterized by a remission of the psychotic symptoms over several days (mean: 1 week), with or without neuroleptic treatment. The majority of the patients suffer from complex partial seizures with frequent psychic auras that secondarily become generalized. In the majority of cases, prepsychotic EEG abnormalities persist during the psychosis. Frequent bitemporal foci are recorded on the EEG and MRI abnormalities (including mesial temporal sclerosis) are seen in more than half of the cases. The results of clinical, morphologic and metabolic available studies will be briefly discussed.     

Familial aggregation of psychotic symptoms in Huntington's disease

OBJECTIVE: The mutation responsible for Huntington's disease is an elongated and unstable trinucleotide (CAG) repeat on the short arm of chromosome 4. Psychotic symptoms are more common in patients with Huntington's disease than in the general population. This study explored the relationship of psychosis in Huntington's disease patients with the number of CAG repeats and family history of psychosis. METHOD: Forty-four patients with Huntington's disease, 22 with and 22 without psychotic symptoms, were recruited from two university-affiliated medical genetics clinics in Seattle and Vancouver, B.C. Psychiatric assessments of the subjects were made through chart review, and diagnoses were validated by structured interviews in a subset of patients. The demographic and clinical characteristics of the psychotic and nonpsychotic patients were compared. RESULTS: The two groups did not differ in demographic and clinical characteristics, except that subjects with psychosis were significantly more likely than nonpsychotic subjects to have a first-degree relative with psychosis. In eight of nine families in which Huntington's disease probands with psychosis had a first-degree relative with psychosis, the relative's psychosis co-occurred with Huntington's disease. In the Huntington's disease probands with psychosis, the onset of psychosis correlated with the onset of the neurological symptoms of Huntington's disease, and the age at onset of psychosis was lower in probands with a higher number of CAG repeats. CONCLUSIONS: Patients with Huntington's disease and psychotic symptoms may have a familial predisposition to develop psychosis. This finding suggests that other genetic factors may influence susceptibility to a particular phenotype precipitated by CAG expansion in the Huntington's disease gene.     

Effects of psychotic state and task demand on prefrontal function in schizophrenia: an fMRI study of overt verbal fluency

OBJECTIVE: Impaired prefrontal cortical function is regarded as a central feature of schizophrenia. Although many neuroimaging studies have found evidence of abnormal prefrontal activation when patients with schizophrenia perform cognitive tasks, the extent to which this abnormality depends on the presence of active psychotic symptoms and on the demands of the task is unclear. The authors tested the hypothesis that prefrontal functional abnormalities in schizophrenia would be more evident in patients with active psychosis than in patients who were in remission and would become more apparent in the face of increasing task demands. METHOD: The authors used functional magnetic resonance imaging (fMRI) to examine prefrontal cortical activity during a paced letter verbal fluency task in three groups of subjects: acutely psychotic patients with schizophrenia, schizophrenia patients in remission, and healthy volunteers. Online subject performance was measured by utilizing a clustered fMRI acquisition sequence that allowed overt verbal responses to be made in the relative absence of scanner noise. RESULTS: Patients with schizophrenia showed less activation than the healthy comparison subjects in the anterior cingulate and the inferior frontal and right middle frontal cortices, independent of psychotic state and task demand. Acutely psychotic patients showed less activation than the healthy comparison subjects, but these differences were less marked than the differences between the patients in remission and the healthy comparison subjects. Acutely psychotic patients had less activation than the comparison subjects in the anterior cingulate but no significant difference in lateral prefrontal activation. Increasing task demand led to greater anterior cingulate and middle frontal activation in patients with active psychosis than in patients in remission. CONCLUSIONS: Schizophrenia is associated with impaired prefrontal function, but its manifestation depends on the severity of psychotic symptoms and the level of task difficulty.     

Thought disorder. A function of schizophrenia, mania, or psychosis?

Does thought disorder emerge solely as a function of psychosis, or is it a function of diagnosis? The present research investigated whether thought disorder is more frequent in specific diagnostic groups, such as schizophrenia and mania, than in other types of psychotic disorders. The frequency and severity of positive thought disorder was assessed in 324 Research Diagnostic Criteria and DSM-III schizophrenics, manics, other psychotic patients, and nonpsychotic patients, and a normal comparison group. Fifty-seven percent of the sample were first hospital admissions. Patients were tested at the acute phase of their disorder, within the first 2 weeks of hospitalization, with three cognitive tests. Scores from these three tests were scaled to obtain a composite index of the severity of positive thought disorder. Diagnostic factors were more salient to the severity of disordered thinking than was psychosis. Thought disorder was significantly more frequent in schizophrenia and mania than in other psychotic disorders (p less than .05). The frequency of patients with severe thought disorder was reduced as one moved down the hierarchy of manic, schizophrenic, schizoaffective, and depressed psychotic disturbances (p less than .001). Rather surprisingly, the current research suggests that nonpsychotic manic patients may be as thought disordered as psychotic manic patients at acute phases of disturbance. This would indicate that the presence of positive thought disorder in mania is not primarily a function of most of these patients' being psychotic at the acute phase of disturbance. Thought disorder was not simply a function of psychosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnostic subtypes of bipolar disorder in older versus younger adults

OBJECTIVE: To investigate differences in diagnostic subtypes of bipolar disorder as according to ICD-10 between patients whose first contact with psychiatric health care occurs late in life (over 50 years of age) and patients who have first contact earlier in life (50 years of age or below). METHODS: From 1994 to 2002 all patients who received a diagnosis of a manic episode or bipolar disorder at initial contact with the mental healthcare system, whether outpatient or inpatient, were identified in Denmark's nationwide register. RESULTS: A total of 852 (49.6%) patients, who were over age 50, and 867 patients, who were 50 or below, received a diagnosis of a manic episode or bipolar disorder at the first contact ever. Older inpatients presented with psychotic symptoms (35.4%) significantly less than younger inpatients (42.6%) due specifically to a lower prevalence of manic episodes with psychotic symptoms. Conversely, older inpatients more often presented with severe depressive episodes with psychotic symptoms than younger inpatients (32.0% versus 17.0%). Among outpatients, no significant differences were found between patients older than 50 years and patients 50 years of age or younger. However, a bimodal distribution of age at first outpatient contact was found with an intermode of 65 years and outpatients older than 65 years more often presented with severe depressive episodes with psychosis. CONCLUSIONS: Bipolar patients who are older at first psychiatric hospitalization (>50 years) present less with psychotic manic episodes and more with severe depressive episodes with psychosis than younger patients. The distribution of age at first outpatient contact is bimodal with an intermode of 65 years and outpatients older than 65 years more often present with severe depressive episodes with psychosis.     

Psychotic reactivity in borderline personality disorder

Glaser J‐P, Van Os J, Thewissen V, Myin‐Germeys I. Psychotic reactivity in borderline personality disorder. Objective: To investigate the stress relatedness and paranoia specificity of psychosis in borderline personality disorder (BPD). Method: Fifty‐six borderline patients, 38 patients with cluster C personality disorder, 81 patients with psychotic disorder and 49 healthy controls were studied with the experience sampling method (a structured diary technique) to assess: i) appraised subjective stress and ii) intensity of psychotic experiences. Results: All patient groups experienced significantly more increases in psychotic experiences in relation to daily life stress than healthy controls, borderline patients displaying the strongest reactivity. Borderline patients, moreover, reported significantly more hallucinatory reactivity than healthy controls and subjects with cluster C personality disorder. Paranoid reactivity to daily life stress did not differ between the patient groups. Conclusion: These results are the first to ecologically validate stress‐related psychosis in BPD. However, psychotic reactivity was not limited to expression of paranoia but involved a broader range of psychotic experiences including hallucinations.     

Elevated rates of psychosis among treatment-seeking Hispanic patients with major depression

It is unknown whether rates of psychosis differ among depressed patients of various races and ethnic groups. In the present study, we sought to determine whether Hispanic patients with major depression who present for treatment are more likely to report psychotic symptoms than whites, even after controlling for multiple potential confounding factors. Fifteen hundred patients presenting to the Rhode Island Hospital Department of Psychiatry's outpatient practice underwent standardized diagnostic evaluations. Rates of psychosis were compared among Hispanic patients diagnosed with a current major depressive disorder and a white control group closely matched on several key demographic and clinical variables. Comparison rates of psychosis were also made with other ethnic groups. Rates of psychosis were significantly higher in 22 Hispanic patients diagnosed with depression (27.3%) compared with a closely matched white control group (N = 44; 6.8%; chi = 5.2; df = 1; p = .02). Rates of psychosis were also significantly higher in Hispanics than in Portuguese patients, but not blacks, although the former cohort differed in several key demographic and clinical variables. The study suggests that Hispanic patients with major depression who present for treatment may be more likely than whites to report psychotic symptoms. It remains unclear whether these reports represent true psychosis or culturally influenced idioms of distress.     

Obsessive-compulsive and panic symptoms in patients with first-admission psychosis

OBJECTIVE: The occurrence, persistence and specificity of the association between comorbid obsessive-compulsive and panic symptoms and three psychotic disorders--schizophrenia/schizoaffective disorder, bipolar disorder with psychosis, and major depression with psychosis--were examined in a first-admission, epidemiologically defined group of patients with psychotic symptoms. METHOD: The Structured Clinical Interview for DSM-III-R obsessive-compulsive and panic modules were administered at baseline and 24-month follow-up to patients with schizophrenia/schizoaffective disorder (N=225), bipolar disorder with psychosis (N=138), and major depression with psychosis (N=87) participating in the Suffolk County (N.Y.) Mental Health Project. The rates of subsyndromal symptoms and disorder criteria met were compared across the three psychosis groups. Recognition and treatment of anxiety symptoms at initial discharge and impact of the baseline presence of anxiety symptoms on 24-month clinical status were also examined. RESULTS: Obsessive-compulsive and panic symptoms were present at baseline in 10%-20% of all three groups. There was no specific association between obsessive-compulsive symptoms and any specific psychosis diagnosis; however, women with major depression with psychosis had a significantly higher rate of panic symptoms than the other two groups, and schizophrenia/schizoaffective disorder patients with baseline panic symptoms were significantly more likely to exhibit positive symptoms of psychosis after 24 months. CONCLUSIONS: The authors found no specific association between obsessive-compulsive symptoms and diagnosis early in the illness course, but the finding of an association between panic symptoms and psychotic depression among female patients and between baseline panic and positive psychotic symptoms in schizophrenia/schizoaffective disorder patients at 24 months suggests the need for further study.     

The course of psychosis in early phases of schizophrenia

To study the course of psychosis in early schizophrenia, the authors assessed 111 patients at hospitalization and at one or two follow-ups. The course of psychosis was analyzed separately for broad (DSM-II) and narrow (DSM-III) concepts of schizophrenia. The patients diagnosed with DSM-II improved in psychosis between the first and second follow-ups. Those also diagnosed with DSM-III showed more persistent psychosis; 40% were psychotic at both follow-ups. A subgroup of patients showed improvement in psychosis even after several years of sustained symptoms. The authors discuss the implications of the data for views about the persistence of psychotic symptoms.     

Cannabis use and outcome of recent onset psychosis.

PURPOSE: To test the hypothesis that recent onset psychotic patients who use cannabis will have psychotic symptoms that are more severe and more persistent than those who do not use cannabis. SUBJECTS AND METHODS: We carried out a 4-year follow-up study of a cohort of 119 patients with recent onset of psychosis. The patients were divided into four groups according to duration of cannabis use, taking index admission and follow-up as reference points. RESULTS: Those subjects who persisted in the use of cannabis had more positive (but not negative) symptoms and a more continuous illness at follow-up. LIMITATIONS: The main limitations of the study were: the relatively small sample size, and that the excess of male subjects and the presence of cannabis induced psychosis could have a confusing impact on the interpretation of the results. CONCLUSION: It is possible that psychotic patients who use cannabis are at a greater risk of a more continuous illness with more positive symptoms than those who do not.