EEG spectral abnormalities and psychosis as predictors of cognitive and functional decline in probable Alzheimer's disease

We examined whether either psychotic features (e.g., delusions and hallucinations) or EEG abnormalities are associated with more rapid progression of Alzheimer's disease (AD). AD patients with psychosis have exhibited more EEG abnormalities than those without psychosis, and both abnormal EEG and psychosis have been noted to be predictors of functional and cognitive decline in AD. Ninety-five probable AD patients participating in a longitudinal study of dementia had an EEG and a semistructured psychiatric interview at baseline. Using EEG spectral analysis, we classified records as normal/abnormal based on the parasagittal mean frequency. Patients with abnormal EEGs were more functionally (e.g., Blessed Rating Scale for activities of daily living) and cognitively (e.g., Mini-Mental State) impaired than patients with normal EEG. AD patients with psychosis were only more functionally impaired than patients without psychosis. A two-factor analysis showed no interaction between abnormal EEG and psychosis. In addition, using a Cox proportional hazard model adjusted for age and education, the presence of an abnormal EEG or psychotic symptom at study entry was associated with higher risk of reaching severe cognitive and functional impairment during follow-up. Neither abnormal EEG nor the presence of psychosis predicted death. These results indicate that both abnormal EEG and psychosis are independent predictors of disease progression but not of physical survival.     

Drug abuse and suicidal tendencies

Among the psychotic symptoms in juvenile drug-consumers one can find autonomous, i.e. drug-independent developments, whose connection with the drug-abuse is to be assessed in differing ways. A beginning psychosis can be modified in its actual symptoms by drug-consumption. On the other hand one must consider the manifestation of a latent psychosis or purely symptomatic psychosis, which, in its symptoms, can hardly be distinguished from schizophrenia. Finally drug-induced personality-changes can develop together with secondary psychotic symptoms. Psychotic symptoms are determined and influenced in a varying degree by drugs. Both after short drug-consumption and after a longer drug-anamnesis with polytoxicomanic symptoms psychotic syndromes can be discovered. Even the initial psychotic symptoms can hint at an adverse development and a bad prognosis. Sometimes the drug-experiences conceal the autonomous development of the psychosis, which, as a rule, shows predominantly schizophrenic symptoms. In addition to a quick change of the actual symptoms, acute states of confusion and depressive-suicidal syndromes, flash-back and horror-trip phenomena, closely connected with the psychotic experience, and a schizophrenic colouring of affective psychoses can be found as frequently drug-induced modifications of the psychotic symptoms. Furthermore one finds an increase of symptoms and of the psychotic episodes in the case of psychoses of the schizophrenic variety which have already begun. Grave personality changes with psychotic symptoms after chronic drug-abuse can cause differential-diagnostic difficulties.     

Cocaine: performance drug of the '90s? Morphologic and criminal sociologic aspects

The drug fatalities handled by the Berlin forensic science institutes from 1992 to 1995 were analyzed with the help of post-mortem records and investigative files in order to ascertain the extent to which deaths showing positive proof of cocaine differ from previously-known drug fatalities from a morphological and a sociological point of view. Additionally, in numerous cases it was possible to have recourse to medical records and interviews with relatives. In analysing individual cases it could be established that only a small proportion of those who had died from drug-related causes and who were found with positive proof of cocaine had been affected by pure cocaine intoxication. In most cases consumption of cocaine was irregular. Predominantly, cases of combined intoxication involving opiate-containing substances were found. Cocaine has lost some of its exclusivity and met with wider acceptance among drug addicts of the opiate-type. Morphologically speaking, findings among drug addicts of the cocaine-type are becoming increasingly less specific; in particular, infectious diseases (e.g. hepatitis) are being observed more rarely. Our results point to the fact that the operating methods of appropriate treatment institutions must be modified with respect to their work with addicts using substitutes.     

Reversal of phencyclidine-induced hyperactivity by glycine and the glycine uptake inhibitor glycyldodecylamide

Phencyclidine (PCP) induces a psychotic state that closely resembles schizophrenia. In preclinical studies, PCP has been shown to induce its unique behavioral effects by blocking excitatory neurotransmission mediated at the N-methyl-D-aspartate (NMDA) receptors, suggesting that agents which potentiate NMDA receptor-mediated neurotransmission might have clinically beneficial effects. The present study demonstrates that the NMDA co-agonist glycine inhibits rodent hyperactivity induced by PCP, but not amphetamine. Glycyldodecylamide, a compound that blocks neuronal glycine uptake and which may therefore increase intrasynaptic glycine levels, inhibits PCP-induced hyperactivity more potently than glycine. These results complement recent clinical studies with glycine and suggest that glycine-uptake inhibitors, as well as glycine, may be beneficial in the treatment of PCP-induced psychosis and schizophrenia.     

Does chronic psychosis due to amphetamines abuse exist? Study of 25 drug addicts

The development of a psychotic process was noted in seven amphetamine addicts who had been seen over a period of several years before onset of the psychosis and who had no psychotic tendencies before the addiction. This group was compared with two from the standpoint of the symptomatology of acute psychosis; i.e. acute psychotic episodes under the effects of amphetamines in individuals who were not psychotic before addiction and who were cured at present, and acute psychotic episodes under the effects of amphetamines in individuals who were psychotic at the time of becoming amphetamine addicts. This comparative study attempts to define the signs which precede the development of a chronic psychosis and includes a discussion concerning the clinical picture and its correlation with the pre-existent personality.     

Daily injections of fluoxetine induce dose-dependent desensitization of hypothalamic 5-HT1A receptors: reductions in neuroendocrine responses to 8-OH-DPAT and in levels of Gz and Gi proteins

BACKGROUND: Overall and left temporal scalp area reductions of P300 have been demonstrated in schizophrenia. P300 amplitude and topography in psychotic affective disorder, a crucial comparison in assessing the specificity of P300 abnormalities to schizophrenia, are not well studied. METHODS: P300 was recorded from 35 schizophrenic, 20 psychotic manic, and 30 control subjects. All were right-handed men. RESULTS: P300 was reduced in both psychotic groups relative to control subjects. Anteroposterior P300 topography differed between patient groups, with schizophrenic subjects showing posterior reduction and bipolar subjects showing anterior reduction. Schizophrenic subjects showed an abnormal asymmetry, with smaller P300 over the left temporal scalp site than the right. Both bipolar and control subjects showed a left greater than right asymmetry. CONCLUSIONS: Widespread auditory P300 reductions were present in schizophrenia and bipolar disorder with psychosis, but subtle topographic differences were present in the two diseases. Although unequivocal knowledge of neural generators cannot be derived from topography alone, differences in topography imply different generator configurations. Based on previous studies, the posterior P300 reductions in schizophrenia may reflect abnormalities of a generator located in the left superior temporal gyrus. The frontal reductions in bipolar psychosis may reflect abnormalities in a hypothetical frontal generator, consonant with reports of altered frontal lobe function in mania.     

The etiologic heterogeneity of schizophrenia

Evidence is increasing in support of the etiologic heterogeneity of schizophrenia. Five distinct diseases/disorders are suggested in this paper, and the relevant studies are reviewed. Familial forms of the disorder include a dopamine psychosis (supported by research documenting both altered dopamine activity and early neuroleptic response among some schizophrenic patients), a neurodegenerative psychosis (supported by investigations that document ongoing change in ventricular brain ratio, elevation of products of cell membrane catabolism within the central nervous system, and age-progressive third ventricle enlargement accompanied by delayed response to neuroleptics), and a neurodevelopmental psychosis (supported by evidence of static enlarged ventricles in some schizophrenic patients and neurological soft signs in high-risk offspring of schizophrenic individuals). Nonfamilial forms include a neurodevelopmental psychosis (supported by evidence of neurodevelopmental abnormalities triggered by neurotropic viruses, radiation, or anoxia) and a lithium-responsive psychosis (supported by evidence of a subgroup of psychotic patients who have low risk of either psychosis or mania in their pedigrees and respond to lithium).     

Movement abnormalities predict conversion to Axis I psychosis among prodromal adolescents.

Evidence suggests that movement abnormalities are a precursor of psychosis. The link between movement abnormalities and psychotic disorders is presumed to reflect common neural mechanisms that influence both motor functions and vulnerability to psychosis. The authors coded movement abnormalities from videotapes of 40 adolescents at risk for psychosis (designated prodromal on the Structured Interview for Prodromal Symptoms; T. J. Miller et al., 2002). Following initial assessment, participants were evaluated for diagnostic status at 4 times annually. Ten participants converted to an Axis I psychosis (e.g., schizophrenia) over the 4-year period. Comparisons of converted and nonconverted participants at baseline indicated that the groups did not differ on demographic characteristics or levels of prodromal symptomatology, but those who converted exhibited significantly more movement abnormalities. Movement abnormalities and prodromal symptoms were strongly associated and logistic regression analyses indicated that abnormalities in the face and upper body regions were most predictive of conversion. Findings suggest that individuals with elevated movement abnormalities may represent a subgroup of prodromal adolescents who are at the highest risk for conversion. The implications for neural mechanisms and for identifying candidates for preventive intervention are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Self-experienced vulnerability, prodromic symptoms and coping strategies before schizophrenic and affective episodes

For the first time, the present study explores self-experienced vulnerability, prodromal symptoms and coping strategies preceding schizophrenic and affective episodes. 33 schizophrenic and 29 depressive patients were assessed retrospectively for preepisodic alterations by means of the "Bonn Scale for the Assessment of Basic Symptoms- BSABS" after complete recovery from the acute episode. 97% of the schizophrenic and 93% of the depressive patients showed preepisodic alterations. In the schizophrenic group the first alteration occurred with a median of 10 weeks and in the depressive group with a median of 18 weeks before the onset of the acute episode. With regard to self-experienced vulnerability depressive cases were significantly less tolerant to stress, i.e work under time pressure or unusual, unexpected requirements. With regard to prodromal symptoms schizophrenics showed significantly more often interpersonal irritation and certain perception and thought disturbances, whereas depressive patients reported more often adynamia and certain disturbances of proprioception. 73% of the schizophrenic patients and 90% of the depressive patients reacted to early symptoms with coping strategies. The preepisodic alterations in schizophrenic patients could be described in terms of mild psychotic productivity, early symptoms of depressive patients could be described as a mild depressive syndrome. Prospective studies are necessary to show if assessment of mild psychotic productivity could be used for early diagnosis and early intervention in schizophrenia.     

Do atypical antipsychotic medications favorably alter the long-term course of schizophrenia?

Schizophrenia is characterized by the greatest degree of clinical deterioration in the first decade following onset of psychosis; in fact, deterioration begins even prior to the onset of frank psychotic symptomatology. While somewhat controversial, it appears that effective early antipsychotic treatment might limit the extent of such deterioration. The newer, atypical antipsychotics such as clozapine, risperidone, olanzapine and quetiapine appear to have antipsychotic efficacy at least equal to the traditional neuroleptics, but with a much more favorable side effect profile. Clozapine is also effective in treating neuroleptic-refractory schizophrenic patients. Data suggest that in comparison to conventional agents, treatment with atypical antipsychotics may be associated with a more benign course of schizophrenic illness. Whether these atypical antipsychotics are associated with greater efficacy in limiting clinical deterioration in schizophrenic illness than traditional neuroleptics is, however, unclear. The following questions will be addressed in this paper: (i) Do atypical antipsychotics differ from traditional neuroleptics in modifying the natural course of symptomatology in schizophrenic illness? (ii) Do atypical antipsychotics differ from typical neuroleptics in modifying the natural course of neurobiological and cognitive abnormalities in schizophrenic illness? (iii) Do atypical antipsychotics differ from typical neuroleptics in modifying the natural course of psychosocial dysfunction in schizophrenic illness? (iv) Are there differences between typical and atypical antipsychotics with regard to their effects on the cost of care and resource utilization? The implications of the answers to these questions for the long-term treatment of schizophrenia will be discussed.     

Handedness in first-episode psychotic patients and their first-degree biological relatives.

We evaluated the handedness of 58 schizophrenia patients and 54 of their relatives, 23 patients with major depression with psychosis and 24 of their relatives, 36 patients with bipolar psychosis and 33 of their relatives, and 119 nonpsychiatric Ss and 42 of their relatives. Computerized tomography measures were also available for a subset of the psychotic patients. The schizophrenia patients were significantly more left-handed than any of the other groups, and increased sinistrality was also associated with larger lateral ventricle to brain area ratios. The relatives of the schizophrenia patients did not significantly differ on handedness from either the relatives of the affective psychosis patients or the nonpsychiatric Ss. Findings do not support the notion that left-handedness in schizophrenia is genetically influenced. More research with larger family member data sets is warranted to further explore this possibility. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pretreatment plasma homovanillic acid in schizophrenia and schizoaffective disorder: the influence of demographic variables and the inpatient drug-free period

BACKGROUND: The relationship between plasma homovanillic acid (pHVA) and schizophrenic symptoms has not been conclusively determined. We reexamine pHVA levels in a new sample of patients with emphasis on demographic variables and the drug-free period. METHODS: Plasma HVA levels were studied in 54 schizophrenic and schizoaffective-disordered, drug-free inpatients suffering from a psychotic exacerbation. RESULTS: A significant correlation was observed between pHVA levels and the number of inpatient drug-free days in the total sample, as well as the schizophrenic patient subsample. Further, pHVA was significantly and positively correlated with the duration of illness in the schizophrenic patient subsample. Plasma HVA correlations with behavior, as measured by Brief Psychiatric Rating Scale factors (anxiety/depression and hostility/suspiciousness), emerged only when considering schizophrenic patients drug-free for more than 2 weeks. No correlation was found between pHVA and the age of illness onset or the duration of the delay of treatment of the first psychotic episode. CONCLUSIONS: The effects of antipsychotic withdrawal on levels of pHVA in clinical populations may have to be examined and controlled for in future studies attempting to study the relationship between this metabolite and behavior in acutely ill, drug-free schizophrenic patients.     

Prenatal and perinatal risk factors for schizophrenia, affective psychosis, and reactive psychosis of early onset: case-control study

OBJECTIVE: To examine prenatal and perinatal risk factors for subsequent development of schizophrenia and affective and reactive psychosis. DESIGN: Three population based, case-control studies conducted within a Sweden-wide cohort of all children born during 1973-9. This was done by linking individual data from the Swedish birth register, which represents 99% of all births in Sweden, to the Swedish inpatient register. SUBJECTS: Patients listed in inpatient register as having been first admitted to hospital aged 15-21 years with a main diagnosis of schizophrenia (n=167), affective psychosis (n=198), or reactive psychosis (n=292). For each case, five controls were selected. MAIN OUTCOME MEASURES: Risks of schizophrenia and affective and reactive psychosis in relation to pregnancy and perinatal characteristics. RESULTS: Schizophrenia was positively associated with multiparity (odds ratio 2.0), maternal bleeding during pregnancy (odds ratio 3.5), and birth in late winter (odds ratio 1.4). Affective psychosis was associated with uterine atony (odds ratio 2.2) and late winter birth (odds ratio 1.5). Reactive psychosis was related to multiparity (odds ratio 2.1). An increased risk for schizophrenia was found in boys who were small for their gestational age at birth (odds ratio 3.2), who were number four or more in birth order (odds ratio 3.6), and whose mothers had had bleeding during late pregnancy (odds ratio 4.0). CONCLUSIONS: A few specific pregnancy and perinatal factors were associated with the subsequent development of psychotic disorder, particularly schizophrenia, in early adult life. The association of small size for gestational age and bleeding during pregnancy with increased risk of early onset schizophrenia among males could reflect placental insufficiency.     

Social context and perceived effects of drugs on sexual behavior among individuals who use both heroin and cocaine.

Researchers have identified the association between the use of cocaine and sexual behavior as an important risk factor for HIV infection and have attempted to elucidate the nature of this association. Several lines of research have suggested that facilitation of sexual behavior during intoxication with cocaine may be because of the direct pharmacological effects of the drug (e.g., increase in sexual desire), whereas others have pointed to the importance of factors related to the context of drug use (e.g., opportunities for sexual behavior, expectations about the effects of the drug, social norms). The present study explored the perceived effects of cocaine and heroin on sexual behavior, as well as the social context of drug use as a function of drug type (cocaine vs. heroin), among 46 inner-city drug users who reported a history of regular use of both crack cocaine and heroin. Results indicated that compared to heroin, cocaine had deleterious effects on participants' perceived sexual desire and performance. Despite such deleterious effects on sexual behavior, cocaine was more frequently used with an intimate partner than heroin. Furthermore, participants did not differ in the extent to which they used the two drugs in other social contexts (e.g., with friends, family, or neighbors). These preliminary results suggest that the relationship between cocaine and sexual behavior, especially among long-term cocaine users, may be facilitated by opportunities for sex that exist in the context of cocaine use, rather than by the pharmacological effects of the drug. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sources of diagnostic uncertainty for chronically psychotic cocaine abusers

OBJECTIVE: This study determined the sources and frequency of diagnostic uncertainty for patients with chronic psychosis and active cocaine abuse or dependence and assessed the usefulness of prospective follow-up in clarifying diagnosis. METHODS: A total of 165 male patients with chronic psychoses and cocaine abuse or dependence on inpatient units of a Veterans Affairs medical center were evaluated using the Structured Clinical Interview for DSM-III-R (SCID-R), urine tests, hospital records, and interviews with collateral sources. An algorithm allowing key SCID-R items and diagnostic criteria to be designated as provisionally met or uncertain was applied, resulting in a provisional diagnosis and a list of alternate diagnoses. The assessment was repeated 18 months later in an attempt to resolve diagnostic uncertainty. RESULTS: In 30 cases (18 percent), initial assessment produced a definitive diagnosis, including 21 cases of schizophrenia, six of schizoaffective disorder, and three of psychostimulant-induced psychotic disorder. In the other 135 cases, a definitive diagnosis could not be reached because of one or more sources of diagnostic uncertainty, including insufficient periods of abstinence (78 percent), poor memory (24 percent), and inconsistent reporting (20 percent). Reassessment at 18 months led to definitive diagnoses in 12 additional cases. CONCLUSIONS: It was frequently difficult to distinguish schizophrenia from chronic substance-induced psychoses. Rather than concluding prematurely that psychotic symptoms are, or are not, substance induced, clinicians should initiate treatment of both psychosis and the substance use disorder in uncertain cases. The persistence or resolution of psychosis during abstinence and additional history from the stabilized patient or collateral sources may clarify the diagnosis.     

In experimental diabetes the decrease in the eye of lens carnitine levels is an early important and selective event

The relationship between a history of substance use disorder and the early course of psychotic illness was examined in 96 subjects with schizophrenia and 106 subjects with affective psychosis followed in the Suffolk County Mental Health Project, a longitudinal study of first-admission psychosis. Subjects received a structured diagnostic interview and clinical ratings at baseline assessment and again 6 months later. The 6-month assessment included information about treatment received during the interval. A lifetime history of substance use disorder was associated with worse clinical functioning at 6 months for schizophrenia subjects, but not for those with affective psychosis. There were no significant associations of substance use disorder with type of treatment during the interval or with self-reported compliance with medication. Schizophrenia subjects were more likely than subjects with affective psychosis to report cannabis use during the interval and to meet criteria for cannabis use disorder.     

Child abuse and psychosis: A literature review and implications for professional practice.

This review summarizes the research demonstrating the relationships of childhood abuse to psychosis and schizophrenia and raises the possibility that the relationships may be causal. Six ways in which the relationship between child abuse and psychosis can be minimized are identified: (a) excluding psychotic individuals from studies; (b) relying on records of childhood abuse rather than asking patients; (c) ignoring relevant studies; (d) reinterpreting psychotic symptoms as nonpsychotic where abuse is identified, thereby avoiding diagnoses such as schizophrenia; (e) positing spurious intervening variables; and (f) adhering rigidly to a biomedical model. Implications for professional practice, at the policy and clinical levels, are presented. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Schizophrenic symptoms, work adjustment, and behavioral family therapy.

Investigated work adjustment among 41 recently exacerbated patients (aged 21–42 yrs) with schizophrenia who were randomly assigned to receive either customary care alone or behavioral family therapy (BFT) and customary care. At baseline, most Ss were unemployed and evidenced poor work adjustment. Negative schizophrenic symptoms were more strongly associated with current work dysfunction than were indices of other psychopathology. At 1 yr, significantly fewer Ss participating in BFT had evidenced psychotic exacerbations. However, vocational adjustment in both groups was still poor, with few benefits of BFT on work functioning noted. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hypofrontality revisited: a high resolution single photon emission computed tomography study in schizophrenia

Hypofrontality or reduced activity in the prefrontal cortex, measured as reduced frontal perfusion or glucose uptake, has gained the status of an established finding in the medical literature on schizophrenia. Many relevant studies, however, have potential sources of bias, such as small subject numbers, or unreliable performance of activation tasks by the patients during the scanning procedure. Seventy patients with non-affective and non-organic psychoses were recruited--most qualifying for DSM III-R schizophrenia or schizophreniform psychosis (n = 60)--together with 20 healthy volunteers. They underwent single photon emission computed tomography with 99mTc-exametazime, carried out at rest. Tracer uptake was normalised to the occipital cortex. Group differences in tracer uptake were predicted in anterior regions of interest (prefrontal cortex and mesial frontal/cingulate cortex). Actively psychotic (including schizophrenic) patients not taking any drugs showed increased uptake in the prefrontal cortex. Reduced tracer uptake occurred in the mesial frontal cortex of schizophrenic patients, particularly if they were taking drugs. Relatively increased prefrontal tracer uptake associated with relatively decreased mesial frontal uptake characterised the patients in comparison with the controls. Generalised hypofrontality is, therefore, not a feature of schizophrenic patients at rest whether taking drugs or not.