Distinct neurophysiological mechanisms for manic and cycloid psychoses: evidence from a P300 study on manic patients

Pathologically asymmetrical P300 fields with right lateralized peaks were described in core schizophrenia as an expression of left-temporal functional deficits, while higher than normal amplitudes were found in cycloid psychosis. This latter finding appeared to be specific for cycloid psychosis and was explained by a generalized cerebral hyperarousal. Based on some psychopathological analogies with cycloid psychosis, and on the comparable pharmacological treatment of the acute episodes, a group of 19 manic patients was investigated immediately after remission and clinical stabilization of an episode. Patients with psychotic features were excluded to avoid overlaps with cycloid psychosis. Patients showed normal P300 amplitudes and no pathological asymmetries of the field, but more posterior positive areas compared to age- and sex-matched controls. This indicates that the neurophysiological changes underlying mania are different from both core schizophrenia and cycloid psychosis. Based on previous three-dimensional source location studies, this finding indicates that disinhibition due to reduced frontal lobe activity, and not hyperarousal, is the basic functional mechanism of manic disorders.     

Hippocampal volume in first-episode psychoses and chronic schizophrenia: a high-resolution magnetic resonance imaging study

BACKGROUND: It has been proposed that the hippocampus is a potential site for a neurodevelopmental lesion in schizophrenia. While smaller hippocampal volumes have been described in chronic schizophrenia, there have been few magnetic resonance imaging studies in first-episode psychosis. Furthermore, no studies have examined the specificity of this finding to first-episode schizophrenia, compared with first-episode affective psychosis. METHODS: Hippocampal and whole-brain volumes were estimated using high-resolution magnetic resonance imaging in 140 controls, 46 patients with chronic schizophrenia, and 32 patients with first-episode psychosis. RESULTS: Patients with chronic schizophrenia and first-episode psychosis had significantly smaller hippocampal volumes as compared with controls. Within the first-episode group, both patients with schizophrenia/schizophreniform psychosis and those with affective psychosis had smaller left hippocampal volumes as compared with controls. Smaller right hippocampal volumes were associated with age and illness duration in patients with chronic schizophrenia. Hippocampal volumes were not correlated with age of illness onset or medication dosage in either patient group. CONCLUSIONS: These data show that smaller hippocampal volumes are present from the onset of illness. While these findings would support the neurodevelopmental model of schizophrenia, the finding of smaller left hippocampal volume in patients with first-episode schizophrenia and affective psychosis does not support the prediction that smaller hippocampi are specific to schizophrenia. The association of smaller right hippocampal volumes with increased illness duration in chronic schizophrenia suggests either that there is further neurodegeneration after illness onset or that bilateral small hippocampi predict chronicity.     

Multi-trait-multi-method assessment of predictive variables of outcome in schizophrenia spectrum disorders. A nosological evaluation

Adopting the nosological hypothesis of functional psychoses, we sought predictive factors for the outcome of two extreme illnesses within the schizophrenia spectrum: cycloid psychosis (N = 23) and hebephrenia (N = 22). The previously completed 5$\text{1}\text{2}$ years follow-through study of both disease entities showed that the two types of psychosis differ distinctly in accordance with nosological expectations. According to the findings of the present study, the predictive factors for the two groups of illness also differ significantly both qualitatively and numerically. The nosospecific predictive factors are probably largely of a biological nature. According to our findings, there is a wider scope for social and psychological predictive factors in cycloid psychosis where the tendency to clinical recovery predominates and where the biologically determined psychosis remains more a foreign body in the life history.     

Genetic markers in cycloid psychosis.

Frequencies of HLA antigens, blood groups, serum groups and red cell enzyme types in patients with cycloid psychosis were compared with those in patients with bipolar psychosis and in normal controls. Patients with cycloid psychosis showed (1) an increased frequency of the Rh-negative type compared to controls, (2) an increased frequency of the K(+) phenotype compared to both bipolar patients and controls, and (3) an increased frequency of the serum group Gc2--1.     

Vergleichsuntersuchung zur Lebensqualität bei Probanden mit zykloiden und schizophrenen Psychosen

BACKGROUND: Cycloid psychoses represent a nosological entity not adequately recognised by contemporary psychiatry. They show full recovery after each episode and thus have a favourable prognosis. METHODS: Course, psychiatric status, social function, and quality of life (QoL) of 33 patients with cycloid psychosis and 44 schizophrenics were compared (CGI, PANSS, GAF, Strauss-Carpenter,WHOQOL-BREF).Also, 48 controls were asked to rate their QoL. RESULTS: The schizophrenics developed symptoms earlier in life (P=0.009) and were hospitalized longer (P=0.001) and more frequently(P=0.01) than patients with cycloid psychosis. The latter showed better scores in the applied scales (P<0.0001). In QoL measures, cycloid psychotic patients were more satisfied than schizophrenic patients in three of four domains(P<0.01).Only in one domain did they differ from controls (P<0.01). CONCLUSION: Cycloid psychoses display better course, outcome, and QoL than schizophrenia.Thus, they appear to present a useful concept deserving more clinical and scientific attention.     

Hippocampal and amygdala volumes according to psychosis stage and diagnosis: a magnetic resonance imaging study of chronic schizophrenia, first-episode psychosis, and ultra-high-risk individuals

CONTEXT: Magnetic resonance imaging studies have identified hippocampal volume reductions in schizophrenia and amygdala volume enlargements in bipolar disorder, suggesting different medial temporal lobe abnormalities in these conditions. These studies have been limited by small samples and the absence of patients early in the course of illness. OBJECTIVE: To investigate hippocampal and amygdala volumes in a large sample of patients with chronic schizophrenia, patients with first-episode psychosis, and patients at ultra-high risk for psychosis compared with control subjects. DESIGN: Cross-sectional comparison between patient groups and controls. SETTING: Individuals with chronic schizophrenia were recruited from a mental health rehabilitation service, and individuals with first-episode psychosis and ultra-high risk were recruited from the ORYGEN Youth Health Service. Control subjects were recruited from the community. PARTICIPANTS: The study population of 473 individuals included 89 with chronic schizophrenia, 162 with first-episode psychosis, 135 at ultra-high risk for psychosis (of whom 39 subsequently developed a psychotic illness), and 87 controls. MAIN OUTCOME MEASURES: Hippocampal, amygdala, whole-brain, and intracranial volumes were estimated on high-resolution magnetic resonance images and compared across groups, including first-episode subgroups. We used 1- and 2-way analysis of variance designs to compare hippocampal and amygdala volumes across groups, correcting for intracranial volume and covarying for age and sex. We investigated the effects of medication and illness duration on structural volumes. RESULTS: Patients with chronic schizophrenia displayed bilateral hippocampal volume reduction. Patients with first-episode schizophrenia but not schizophreniform psychosis displayed left hippocampal volume reduction. The remaining first-episode subgroups had normal hippocampal volumes compared with controls. Amygdala volume enlargement was identified only in first-episode patients with nonschizophrenic psychoses. Patients at ultra-high risk for psychosis had normal baseline hippocampal and amygdala volumes whether or not they subsequently developed a psychotic illness. Structural volumes did not differ between patients taking atypical vs typical antipsychotic medications, and they remained unchanged when patients treated with lithium were excluded from the analysis. CONCLUSIONS: Medial temporal structural changes are not seen until after the onset of a psychotic illness, and the pattern of structural change differs according to the type of psychosis. These findings have important implications for future neurobiological studies of psychotic disorders and emphasize the importance of longitudinal studies examining patients before and after the onset of a psychotic illness.     

Ventral Anterior Cingulate Connectivity Distinguished Nonpsychotic Bipolar Illness From Psychotic Bipolar Disorder and Schizophrenia

Bipolar illness is a debilitating neuropsychiatric disorder associated with alterations in the ventral anterior cingulate cortex (vACC), a brain region thought to regulate emotional behavior. Although recent data-driven functional connectivity studies provide evidence consistent with this possibility, the role of vACC in bipolar illness and its pattern of whole brain connectivity remain unknown. Furthermore, no study has established whether vACC exhibits differential whole brain connectivity in bipolar patients with and without co-occurring psychosis and whether this pattern resembles that found in schizophrenia. We conducted a human resting-state functional connectivity investigation focused on the vACC seed in 73 remitted bipolar I disorder patients (33 with psychosis history), 56 demographically matched healthy comparison subjects, and 73 demographically matched patients with chronic schizophrenia. Psychosis history within the bipolar disorder group corresponded with significant between-group connectivity alterations along the dorsal medial prefrontal surface when using the vACC seed. Patients with psychosis history showed reduced connectivity (Cohen’s d = −0.69), whereas those without psychosis history showed increased vACC coupling (Cohen’s d = 0.8) relative to controls. The vACC connectivity observed in chronic schizophrenia patients was not significantly different from that seen in bipolar patients with psychosis history but was significantly reduced compared with that in bipolar patients without psychosis history. These robust findings reveal complex vACC connectivity alterations in bipolar illness, which suggest differences depending on co-occurrence of lifetime psychosis. The similarities in vACC connectivity patterns in schizophrenia and psychotic bipolar disorder patients may suggest the existence of common mechanisms underlying psychotic symptoms in the two disorders.Key words: bipolar illness, schizophrenia, connectivity, resting-state, medial prefrontal cortex     

Differences in quality of life and course of illness between cycloid and schizophrenic psychoses - a comparative study.

OBJECTIVE: Cycloid psychoses represent a nosological entity not adequately recognised by contemporary psychiatry. They present with full recoveries after each psychotic episode and, thus, have a favourable prognosis. METHOD: To verify this clinical observation course, outcome and quality of life (QoL, measured by the German version of the Lancashire Quality of Life Profile) of 33 patients with cycloid psychosis and 44 schizophrenics were compared after a mean time of 13 years since first hospitalisation. For comparison of objective and subjective QoL measures, 48 healthy controls were included. RESULTS: Concerning the course of their disease, schizophrenics were hospitalised significantly longer and received higher neuroleptic doses than patients with cycloid psychosis. The latter displayed significantly better scores in the CGI, GAF, Strauss-Carpenter-Outcome and PANSS scales. In global QoL measures, cycloid psychotic patients were more satisfied with their QoL than schizophrenic patients, and did not differ significantly from healthy controls. CONCLUSION: Cycloid psychoses seem to exhibit a better prognosis than schizophrenia regarding course, outcome, objective, and subjective aspects of QoL. Thus, they appear to present a useful concept deserving more clinical and scientific attention.     

Uncinate fasciculus abnormalities in recent onset schizophrenia and affective psychosis: A diffusion tensor imaging study

Two of the most frequently investigated regions in diffusion tensor imaging studies in chronic schizophrenia are the uncinate fasciculus (UF) and cingulum bundle (CB). The purpose of the present study was to determine whether UF and CB white matter integrity were altered at the early stage of illness and specific to schizophrenia. Fifteen schizophrenia subjects and 15 affective psychosis within 4 years of first hospitalization (12 patients with schizophrenia and 12 patients with affective psychosis during their first hospitalization), and 15 psychiatrically healthy controls underwent line-scan diffusion tensor imaging. Fractional anisotropy (FA) and mean diffusivity (D_m) were used to quantify water diffusion, and cross-sectional area was defined with a directional threshold method. Bilaterally reduced FA, but not D_m, was present in the UF of schizophrenia compared with healthy controls. Affective psychosis was intermediate between schizophrenia subjects and healthy controls, but not significantly different from either. For CB, there was no significant group difference for FA or D_m. These findings suggest that UF, but not CB, white matter integrity is altered at the early stage of illness in schizophrenia although it may not be specific to schizophrenia. The CB abnormalities reported in chronic schizophrenia may develop during the later course of the disease.     

Increased circulatory dehydroepiandrosterone and dehydroepiandrosterone-sulphate in first-episode schizophrenia: relationship to gender, aggression and symptomatology

Dehydroepiandrosterone (DHEA) is a major circulating neurosteroid in humans and its administration has demonstrated efficacy in the improvement of mood, with increased energy, interest, confidence and activity levels. Since recent findings have suggested the role of neurosteroids in general, and DHEA in particular, in the symptomatology and pharmacotherapy of schizophrenia patients with chronic illness, we investigated DHEA and DHEA-S blood levels in individuals in their first-episode of psychosis in order to exclude effects of age, chronic illness, long-term treatment and institutionalization. Blood levels for DHEA, DHEA-S and cortisol were obtained for 37 first-episode schizophrenia subjects and 27 normal age- and sex-matched controls and correlated with a range of clinical and side-effect rating scales. Baseline DHEA and DHEA-S levels were significantly higher in schizophrenia patients (p<0.05 and p<0.001, respectively). No gender differences were noted in DHEA levels; however, DHEA-S levels were significantly higher in male patients. DHEA-S levels inversely correlated with severity of illness (p<0.05) and aggressive behavior (p<0.05). Patients with higher DHEA-S levels tended to have shorter hospitalizations. Results suggest that individuals in their first-episode of schizophrenia psychosis may develop a neurosteroid response to the first onset of psychosis, which may be associated with a reduction in various adverse clinical features including aggression. Such a putative mechanism may become desensitized with the onset of chronic illness. While preliminary, these results further imply the role of these neurosteroids in the pathophysiology and management of schizophrenia.     

Sex differences in the cortisol response to awakening in recent onset psychosis

A dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis has been suggested as a factor in the etiology and exacerbation of psychosis, but has not been reported consistently. Sex differences are apparent in many aspects of psychotic disorders and may explain some of the equivocation associated with the regulation of the HPA axis in the illness. The present study compared the cortisol response to awakening (CRA) in 27 patients (16 men and 11 women) with recent onset of psychosis (within the past 2 years) and 40 age and gender matched controls. Within the patient group, we also assessed the relationship between the CRA and positive and negative symptoms of psychosis, anxiety and depression. The CRA in patients was not significantly different from controls. However, within the patient group, we observed a significant sex difference, with a blunted cortisol response to awakening in men but not in women (F=7.26; p<0.002). This difference could not be explained by differences between male and female patients in awakening time, medication, or diagnosis of schizophrenia vs. affective psychosis. Cortisol levels were not related to symptom measures. Our findings demonstrate a dysregulation of the HPA axis in male patients with recent onset of psychosis. This sex specificity might be related to and explain in part the unfavorable course of the illness observed in men.     

Neurological deviations in newborns at psychiatric high risk

Neurological deviations on the third to fourth day of life were blindly assessed in 55 offspring of index women with histories of nonorganic psychoses and in 71 offspring of demographically similar control women with no history of psychosis. While the total index group did not differ from the total control group on rates of neurological deviation, the offspring of women with schizophrenia and cycloid psychosis showed more neurological deviations of a diverse nature than did their controls. The offspring of women with affective disorders had rates of deviation that were lower than those of controls and other index diagnostic groups. The differences observed were not sensitive to the narrowness of diagnostic criteria for schizophrenia and affective disorder.     

Physical illness and lifestyle risk factors in people with their first presentation of psychosis

Background There is an increased prevalence of physical illness and poor lifestyle in patients with chronic schizophrenia. It is unclear whether these are present at the onset of psychosis or develop over the course of illness. We aimed to establish whether patients experiencing their first episode of psychosis have worse physical health and lifestyle than community controls without psychosis. Method Eighty-nine patients with new onset illness were compared to age and sex matched controls for self-reported physical illness and cardiovascular and respiratory risk factors. Results Patients reported more physical health complaints, mainly respiratory, compared with age and gender matched controls (odds ratio 2.85, 95% confidence interval 1.2–6.7). Patients were more likely to be cigarette smokers (1.82, 95% CI 1.0–3.3) and eat a fast food diet (1.04, 95% CI 1.0–1.1), but these differences were accounted for by patients’ unemployment status. Conclusions Some risk factors for physical health problems are present at the onset of psychosis, but these may be explained by unemployment.     

Neurological soft signs in obsessive-compulsive disorder: The effect of co-morbid psychosis and evidence for familiality

Patients with obsessive-compulsive disorder (OCD) have increased rates of neurological soft signs (NSS) when compared to healthy controls. However, previous findings have been confounded by the presence of co-morbidity with disorders themselves associated with increased NSS, such as schizophrenia. Moreover, it remains unclear whether NSS in OCD reflect a vulnerability to this disorder. This study aimed to examine: 1) the severity of NSS in patients with OCD alone, in patients with OCD and co-morbid psychosis (schizophrenia or bipolar disorders), and in healthy controls; and b) whether unaffected first-degree relatives of patients with OCD also demonstrate a higher prevalence rate of NSS than healthy controls. NSS were assessed with the Cambridge Neurological Inventory (CNI) in 100 patients with OCD, 38 patients with OCD and psychosis (22 with bipolar disorders and 16 with schizophrenia), and 101 healthy controls. Forty-seven unaffected first-degree relatives of patients with OCD only were also administered the CNI. Patients with OCD showed significantly higher scores in motor coordination and total NSS than controls, and patients with OCD co-morbid with psychosis also showed significantly higher scores in motor coordination and total NSS than controls. Although there were no differences in NSS between patients with OCD only and OCD and psychosis as a whole, patients with OCD co-morbid with schizophrenia showed significantly higher scores in motor coordination than patients with OCD, patients with OCD and bipolar disorder, and healthy controls. Unaffected first-degree relatives only showed a higher prevalence rate than healthy controls in specific motor coordination signs, such as Opposition and Extinction. These findings suggest that patients with OCD exhibit more NSS than healthy controls, and that motor coordination signs may be even more extensive when OCD is co-morbid with psychosis. Some of these abnormalities may be indicative of a vulnerability to these disorders, as indicated by their presence in un-affected first-degree relatives.     

Radiological findings in individuals at high risk of psychosis

OBJECTIVE: To assess the prevalence of radiological magnetic resonance imaging (MRI) findings in individuals at high risk of schizophrenia. METHODS: MRI scans from individuals at high risk of schizophrenia (HR; n = 37) were assessed by a radiologist blind to group status and compared with scans from patients with first episode psychosis (FE; n = 30), depressive controls (DC; n = 17), and healthy controls (HC; n = 26). RESULTS: There was a significantly higher proportion of radiological findings in individuals at high risk of schizophrenia (35%) and patients with first-episode psychosis (40%) than in patients with depression (18%) or healthy controls (12%). These differences were specific to findings regarded as potentially clinically significant as opposed to normal variants; however, there was no indication for medical treatment. CONCLUSIONS: The results suggest that a large proportion of those at high risk of psychosis have radiological findings on MRI scanning, and that the prevalence of radiological findings in this group is similar to that in patients with first episode psychosis.     

Planum temporale and Heschl gyrus volume reduction in schizophrenia: a magnetic resonance imaging study of first-episode patients

BACKGROUND: Magnetic resonance imaging studies in schizophrenia have revealed abnormalities in temporal lobe structures, including the superior temporal gyrus. More specifically, abnormalities have been reported in the posterior superior temporal gyrus, which includes the Heschl gyrus and planum temporale, the latter being an important substrate for language. However, the specificity of the Heschl gyrus and planum temporale structural abnormalities to schizophrenia vs affective psychosis, and the possible confounding roles of chronic morbidity and neuroleptic treatment, remain unclear. METHODS: Magnetic resonance images were acquired using a 1.5-T magnet from 20 first-episode (at first hospitalization) patients with schizophrenia (mean age, 27.3 years), 24 first-episode patients with manic psychosis (mean age, 23.6 years), and 22 controls (mean age, 24.5 years). There was no significant difference in age for the 3 groups. All brain images were uniformly aligned and then reformatted and resampled to yield isotropic voxels. RESULTS: Gray matter volume of the left planum temporale differed among the 3 groups. The patients with schizophrenia had significantly smaller left planum temporale volume than controls (20.0%) and patients with mania (20.0%). Heschl gyrus gray matter volume (left and right) was also reduced in patients with schizophrenia compared with controls (13.1%) and patients with bipolar mania (16.8%). CONCLUSIONS: Compared with controls and patients with bipolar manic psychosis, patients with first-episode schizophrenia showed left planum temporale gray matter volume reduction and bilateral Heschl gyrus gray matter volume reduction. These findings are similar to those reported in patients with chronic schizophrenia and suggest that such abnormalities are present at first episode and are specific to schizophrenia.     

Difference in age of onset of psychosis between epilepsy and schizophrenia

To clarify the nature of psychosis development in epilepsy patients, we studied differences in age of onset of psychosis between epilepsy patients with psychosis (epilepsy-psychosis) and schizophrenia patients. Subjects were 282 patients with epilepsy-psychosis (36 postictal, 224 interictal, and 22 bimodal psychoses) and 612 schizophrenia patients. Age of onset was compared between the schizophrenia group and the whole epilepsy-psychosis group as well as its subgroups. Effects of sex and family history of psychosis on age of onset were also evaluated. Epilepsy patients developed psychosis later (mean age 30.1) than schizophrenia patients (mean age 26.6). Among epilepsy-psychosis subgroups, postictal psychosis and interictal psychosis showed a later onset than schizophrenia. In interictal psychosis, while chronic schizophrenia-like psychosis occurred at similar age compared to schizophrenia, brief episodic psychosis occurred at later age. Epilepsy-psychosis patients showed no sex difference in age of onset, whereas female schizophrenia patients showed a later onset than male schizophrenia patients. Both the epilepsy and schizophrenia patients with family history of psychosis tended to develop psychosis at an earlier age, although this did not reach statistically significant level. The findings of the study suggest that the nature of epilepsy-psychosis is not fully equivalent to that of schizophrenia.     

Dorsolateral prefrontal and superior temporal volume deficits in first–episode psychoses that evolve into schizophrenia

Regions with a likely involvement in schizophrenia may differ between patients with firstepisodes of psychosis respectively with and without evolution into schizophrenia following the initial episode. We have used magnetic resonance imaging (MRI) to assess the volumes of dorsolateral prefrontal (DLPF) and superior temporal gyrus (STG) in a group of 37 first–episode psychotic patients. After an initial MRI study performed by the time of the first episode, the subjects were followed for two years. After this period 22 cases were diagnosed with schizophrenia, while the other 15 did not show clinical evidence for this illness. A Talairach–based tool was used for segmentation and volumetry of the MRI scans. A group of 44 healthy controls was used for comparison and, using lineal regression, to control for the normal effects of age and intracranial volume on the regional parameters of the patients. By the time of their first episode, patients with schizophrenia had significantly less grey matter in the right DLPF and STG regions as compared to both controls and FE without schizophrenia. Nevertheless, these parameters could not predict final diagnosis in a discriminant analysis model. Our findings indicate that subtle structural defects are already found by the time of the first psychotic break in schizophrenia, although clinical implications for these differences seem unclear.     

Nonlinear complexity and spectral analyses of heart rate variability in medicated and unmedicated patients with schizophrenia

OBJECTIVE: Heart rate variability (HRV) reflects functioning of the autonomic nervous system and possibly also regulation by the neural limbic system, abnormalities of which have both figured prominently in various etiological models of schizophrenia, particularly those that address patients' vulnerability to stress in connection to psychosis onset and exacerbation. This study provides data on cardiac functioning in a sample of schizophrenia patients that were either medication free or on atypical antipsychotics, as well as cardiac data on matched healthy controls. We included a medication-free group to investigate whether abnormalities in HRV previously reported in the literature and associated with atypical antipsychotics were solely the effect of medications or whether they might be a feature of the illness (or psychosis) itself. METHOD: We collected 24-hour ECGs on 19 patients and 24 controls. Of the patients, 9 were medication free and 10 were on atypical antipsychotics. All subject groups were matched for age and gender. Patient groups showed equivalent symptom severity and type, as well as duration of illness. We analyzed the data using nonlinear complexity (symbolic dynamic) HRV analyses as well as standard and relative spectral analyses. RESULTS: For the medication-free patients as compared to the healthy controls, our data show decreased R-R intervals during sleep, and abnormal suppression of all frequency ranges, but particularly the low frequency range, which persisted even after adjusting the spectral data for the mean R-R interval. This effect was exacerbated for patients on atypical antipsychotics. Likewise, nonlinear complexity analysis showed significantly impaired HRV for medication-free patients that was exacerbated in the patients on atypical antipsychotics. CONCLUSIONS: Altogether, the data suggest a pattern of significantly decreased cardiac vagal function of patients with schizophrenia as compared to healthy controls, apart from and beyond any differences due to medication side effects. The data additionally confirm earlier reports of a deleterious effect of atypical antipsychotics on HRV, which may exacerbate an underlying vulnerability in patients. These results support previous evidence that autonomic abnormalities may be a core feature of the illness (or psychosis), and that an even more conservative approach to cardiac risk in schizophrenia than previously thought may therefore be clinically appropriate.     

Somatic Care with a Psychotic Disorder. Lower Somatic Health Care Utilization of Patients with a Psychotic Disorder Compared to Other Patient Groups and to Controls Without a Psychiatric Diagnosis

Patients with non-affective psychotic disorders (NAPD) face higher risk of somatic problems and early natural death compared to the general population. Therefore, treatment guidelines for schizophrenia and psychosis stress the importance of monitoring somatic risk factors. This study examined somatic Health Care utilization (HCu) of patients with NAPD compared to non-psychiatric controls and patients with depression, anxiety or bipolar disorders using a large Health Insurance database. Results show lower specialist somatic HCu of patients with NAPD compared to matched controls and also lower percentages for prescribed somatic medication and general practitioner consultations for patients aged ≥60 years and after longer illness duration.