patients with phc are often described as having been reclusive , suspicious , and hostile throughout life . in france in 1911 , ballet found abnormal personality traits in 80% of patients with phc .
however , some patients have a good academic and employment record , even if social isolation may frequently occur . in a french sample of 30 patients with phc ,
the majority of patients were married and had children , but half of them lived alone at the beginning of the illness .
the vast majority of phc patients were working or retired , in contrast to the majority of the group of patients with schizophrenia , who had a mentally handicapped status .
while the majority of cases of phc begin after 30 years , pull and pichot did not base the definition of this disorder on the age at onset , in contrast with the concepts of late - onset schizophrenia and late paraphrenia . in our study ,
the mean age at onset of phc was 50 years , ie , 20 years older than in the schizophrenic groups . in this respect ,
the international lateonset schizophrenia group consensus conference emphasized that categorization by specific age - at - onset ranges was relatively arbitrary with a proposed cutoff of 40 , 45 , 55 , or 60 years . 
 
phc patients are more likely to have hallucinations than schizophrenic patients , particularly when multiple sensory modalities are concerned .
this clinical picture shares common characteristics with late paraphrenia , or late - onset schizophrenia .
specific hallucinations including conversing voices , running commentary auditory hallucinations , and thought echo are characteristic of the phc group .
all these hallucinatory experiences characterized the mental automatism described by de clrambault in 1924 for the isolation of the concept of phc , and are a further important clinical difference from cases of schizophrenia .
the delusions in pch were also often well - systematized and fantastic , with paranoid and persecutory content and the presence of  partition delusions . 
persecution and ideas of reference are found in excess in the phc group , consistent with established features of late paraphrenia or lateonset schizophrenia .
phc patients are also more likely than schizophrenic patients to complain about delusions of being controlled and exposed to thought insertion .
automatism described by de clrambault and were particularly important in the hallucinatory experiences in a variety of sensory modalities for the first isolation of the concept of phc one century ago . the description of positive symptoms and , particularly , the kind of delusions and the modality of hallucinations all share common aspects in phc , late paraphrenia , and late - onset schizophrenia .
the description seems to be more homogeneous and more pronounced in phc patients who have at least one kind of hallucination and always have persecutory delusions .
negative symptoms are very rare in the phc group , while they are much more frequently cited in schizophrenia , particularly for cases with an early onset .
pearlson observed that the occurrence of negative symptoms increased with duration of illness , and decreased with age at onset .
these findings are consistent with the idea that negative or deficit symptoms are characteristic of an early - onset form of schizophrenia , and are not detected in phc .
phc patients were initially described by the absence of formal thought disorder , though in 1961 kay and roth reported incoherence of speech , the use of neologisms , circumstantiality , or irrelevance in 30% of their patients with late paraphrenia , and pearlson et al found thought disorder in 6% of patients with late - onset schizophrenia .
formal thought disorder may not exist in phc , though it is considered to be a core feature of schizophrenia . 

computed tomography and magnetic resonance imaging studies have reported nonspecific structural changes ( higher ventricle / brain ratio , third ventricle volume ) in patients with late - onset psychosis compared with agematched controls .
studies on the density of dopamine d2 receptors ( positron emission tomography [ pet ] or single photon emission computed tomography [ spect ] ) have produced discrepant results . 
 
old age is often associated with reduced sensitivity and acuity of taste , smell , touch , vision , and hearing .
although both auditory ( particularly long - standing conductive deafness ) and visual deficits have been related to the development of paranoid features in old age , this observation may be explained by the reluctance of these patients to seek corrective measures .
however , reports of a significant reduction in psychotic activity after a hearing aid has been fitted indicate that deafness is , at least in part , a predisposing factor for the development of symptoms , even though it is difficult to explain such a complex disorder on the basis of a simple sensory deficit . 
  practically all studies of late - onset schizophrenia and late paraphrenia , or more particularly phc , report a large excess of affected women .
reported female / male ratios range from 6:1 to 45:2 ; in one phc group , bnazet found a 1:7 female / male ratio . 
 
seeman and lang proposed that the higher level of estrogen before the menopause might result in the delayed onset of symptoms in women .
pearlson et al reported an increased density of d2 receptors in lateonset schizophrenia , although a recent attempt to replicate this finding has failed .
estrogens seem to modulate the sensitivity of d2 receptors in brain and , according to some authors , estrogens could have a ncuroleptic - like effect .
moreover , estrogens can reduce the dopamine concentration in the striatum , thereby modulating the sensitivity and the number of dopamine receptors .
estrogens could thus act as a protective factor , delaying the onset of the psychotic syndrome in women .
the menopause could represent a high - risk period in vulnerable women in terms of loss of estrogen .
an alternative hypothesis is that , rather than the existence of a delaying factor detected in all female patients , some vulnerability factors may be involved in a subgroup of patients , with a particular range of age at onset .
for example , in a recent genetic analysis , we observed a significant excess of one d2 receptor gene haplotype in schizophrenic patients , specifically in a subsample of patients with a disease onset occurring after 20 years of age . 
 
another hypothesis is that significant vulnerability genes are differentially expressed among generations , with a milder form and late onset ( such as phc ) in older generations , and a more severe disorder with younger age at onset ( such as schizophrenia ) in younger generations .
if such mutations are involved , and if the phc phenotype is the milder form of the schizophrenia spectrum disorder , we should observe a decreased risk in ascendants ( this is the sherman paradox ) , and an increased risk in descendants .
family , adoption , and twin studies suggest that there are genetic factors in the risk for schizophrenia .
the frequency of schizophrenia in the relative of an affected proband is close to 10% , compared with 1% in the general population .
unfortunately , the literature on familial risk in phc or late - onset schizophrenia is rather sparse , partly because of the difficulty in conducting such family studies in elderly patients who often have few surviving relatives .
moreover , these studies often lack a methodological description for the identification of family members and the definition of illness , including the age at onset . despite these limitations , the risk of schizophrenia in relatives of late - onset schizophrenic probands ranges from 2.3% to 9.8% for siblings and from 0.0% to 4.4% for parents .
thus , it appears that the prevalence of schizophrenia in the first - degree relatives of lateonset schizophrenic probands is greater than in the general population , but lower than in the first - degree relatives of earlier - onset schizophrenic patients .
previous studies showed a trend toward decreasing familial risk schizophrenia with increasing age at onset .
some reports have suggested the existence of a subgroup of affected females with late onset and no family history of schizophrenia .
in addition , later - onset illness is associated with clinical peculiarities ( intensity of delusions and presence of multiple - sense hallucinations , rarity of negative symptoms , or thought disorder ) and a better outcome . only bleuler and post give data on age at onset in relatives , making any definite conclusion difficult to draw . 
  in our sample
, we found that subjects with phc had less familial risk ( 6/501 ) compared with schizophrenic subjects ( 17/418 ) ( =7.70 , df=1 , p=0.006 ) ( table 1 ) .
this difference is mainly explained by the presence of lessaffected sibs in phc patients compared with schizophrenic patients ( 2/83 versus 9/78 ; =5.37 , df=1 , p=0.02 ) and a tendency for less - affected ascendants ( none versus 5/236 ) .
furthermore , we found that age at onset was moderately correlated within families ( p=0.501 , df=15 , p=0.097 ) , highly correlated within sibships ( p=0.629 , df=24 , p=0.004 ) , but not correlated throughout different generations within families ( p=-0.389 , df=16 , p=022 ) .
subjects with phc thus had less family history of schizophrenia than the schizophrenic patients in our sample , but were associated with an increased risk of an earlier and more severe psychotic phenotype ( ie , schizophrenia ) in descendants , without any detected case of phc in the relatives of the proband .
this is compatible with the anticipation effect , which has already been suggested for schizophrenia by many studies . 
 
anticipation describes an inheritance pattern within a pedigree where disease severity increases or age at onset decreases in successive generations .
this phenomenon has been described in nearly 20 neuropsychiatrie disorders such as fragile x syndrome and huntington 's disease . in these disorders
, anticipation has recently been shown to correlate with the expansion of trinucleotide repeat sequences at the disease locus ( figure 1 ) .
these diseases represent a class of disorders caused by unstable dna sequences that can change in each generation , accounting for anticipation .
the discovery in rapid succession of several diseases caused by expansion of triplets raises the possibility that additional neuropsychiatrie disorders with clinical features of anticipation could be candidates .
the common properties of these mutations are the departures from mcndclian inheritance and the highly variable phenotype with wide - ranging age at onset , which are wellknown characteristics of schizophrenia .
more direct analyses of the genome have been made in order to detect large expansion of triplets in severe and early forms of schizophrenia , with conflicting and , above all , negative results .
the complexity of the methods required to detect a specific unstable mutation , and the clinical and genetic heterogeneity of schizophrenia , probably explain the presence of many negative studies and nonreplications of initially positive associations . on the other hand , epidemiological evidence in favor of anticipation
can be considered as very good , because it is based on many different samples and with numerous different methodological strategies .
nevertheless , the relationship between epidemiological anticipation and unstable genes remains to be proven in schizophrenia .
evidence for the anticipation effect is reinforced by the presence of a correlation for age at onset within sibships in our sample , with a younger age at onset in recent generations .
if the phc syndrome is considered as a moderate form of schizophrenia ( with moderate negative features and late age at onset ) , then it could be associated with a low number of triplet repeats ( but above the normal range ) .
the absence of affected ascendants and the 2.4% frequency of affected descendants are in accordance with this hypothesis .
computed tomography and magnetic resonance imaging studies have reported nonspecific structural changes ( higher ventricle / brain ratio , third ventricle volume ) in patients with late - onset psychosis compared with agematched controls .
studies on the density of dopamine d2 receptors ( positron emission tomography [ pet ] or single photon emission computed tomography [ spect ] ) have produced discrepant results . 

old age is often associated with reduced sensitivity and acuity of taste , smell , touch , vision , and hearing .
although both auditory ( particularly long - standing conductive deafness ) and visual deficits have been related to the development of paranoid features in old age , this observation may be explained by the reluctance of these patients to seek corrective measures .
however , reports of a significant reduction in psychotic activity after a hearing aid has been fitted indicate that deafness is , at least in part , a predisposing factor for the development of symptoms , even though it is difficult to explain such a complex disorder on the basis of a simple sensory deficit . 

practically all studies of late - onset schizophrenia and late paraphrenia , or more particularly phc , report a large excess of affected women .
reported female / male ratios range from 6:1 to 45:2 ; in one phc group , bnazet found a 1:7 female / male ratio . 
 
seeman and lang proposed that the higher level of estrogen before the menopause might result in the delayed onset of symptoms in women .
pearlson et al reported an increased density of d2 receptors in lateonset schizophrenia , although a recent attempt to replicate this finding has failed .
estrogens seem to modulate the sensitivity of d2 receptors in brain and , according to some authors , estrogens could have a ncuroleptic - like effect .
moreover , estrogens can reduce the dopamine concentration in the striatum , thereby modulating the sensitivity and the number of dopamine receptors .
estrogens could thus act as a protective factor , delaying the onset of the psychotic syndrome in women .
the menopause could represent a high - risk period in vulnerable women in terms of loss of estrogen .
an alternative hypothesis is that , rather than the existence of a delaying factor detected in all female patients , some vulnerability factors may be involved in a subgroup of patients , with a particular range of age at onset .
for example , in a recent genetic analysis , we observed a significant excess of one d2 receptor gene haplotype in schizophrenic patients , specifically in a subsample of patients with a disease onset occurring after 20 years of age . 
 
another hypothesis is that significant vulnerability genes are differentially expressed among generations , with a milder form and late onset ( such as phc ) in older generations , and a more severe disorder with younger age at onset ( such as schizophrenia ) in younger generations .
if such mutations are involved , and if the phc phenotype is the milder form of the schizophrenia spectrum disorder , we should observe a decreased risk in ascendants ( this is the sherman paradox ) , and an increased risk in descendants .
family , adoption , and twin studies suggest that there are genetic factors in the risk for schizophrenia .
the frequency of schizophrenia in the relative of an affected proband is close to 10% , compared with 1% in the general population .
unfortunately , the literature on familial risk in phc or late - onset schizophrenia is rather sparse , partly because of the difficulty in conducting such family studies in elderly patients who often have few surviving relatives .
moreover , these studies often lack a methodological description for the identification of family members and the definition of illness , including the age at onset . despite these limitations ,
the risk of schizophrenia in relatives of late - onset schizophrenic probands ranges from 2.3% to 9.8% for siblings and from 0.0% to 4.4% for parents .
thus , it appears that the prevalence of schizophrenia in the first - degree relatives of lateonset schizophrenic probands is greater than in the general population , but lower than in the first - degree relatives of earlier - onset schizophrenic patients .
previous studies showed a trend toward decreasing familial risk schizophrenia with increasing age at onset .
some reports have suggested the existence of a subgroup of affected females with late onset and no family history of schizophrenia .
in addition , later - onset illness is associated with clinical peculiarities ( intensity of delusions and presence of multiple - sense hallucinations , rarity of negative symptoms , or thought disorder ) and a better outcome .
only bleuler and post give data on age at onset in relatives , making any definite conclusion difficult to draw . 
  in our sample
, we found that subjects with phc had less familial risk ( 6/501 ) compared with schizophrenic subjects ( 17/418 ) ( =7.70 , df=1 , p=0.006 ) ( table 1 ) .
this difference is mainly explained by the presence of lessaffected sibs in phc patients compared with schizophrenic patients ( 2/83 versus 9/78 ; =5.37 , df=1 , p=0.02 ) and a tendency for less - affected ascendants ( none versus 5/236 ) .
furthermore , we found that age at onset was moderately correlated within families ( p=0.501 , df=15 , p=0.097 ) , highly correlated within sibships ( p=0.629 , df=24 , p=0.004 ) , but not correlated throughout different generations within families ( p=-0.389 , df=16 , p=022 ) .
subjects with phc thus had less family history of schizophrenia than the schizophrenic patients in our sample , but were associated with an increased risk of an earlier and more severe psychotic phenotype ( ie , schizophrenia ) in descendants , without any detected case of phc in the relatives of the proband .
this is compatible with the anticipation effect , which has already been suggested for schizophrenia by many studies . 
 
anticipation describes an inheritance pattern within a pedigree where disease severity increases or age at onset decreases in successive generations .
this phenomenon has been described in nearly 20 neuropsychiatrie disorders such as fragile x syndrome and huntington 's disease . in these disorders
, anticipation has recently been shown to correlate with the expansion of trinucleotide repeat sequences at the disease locus ( figure 1 ) .
these diseases represent a class of disorders caused by unstable dna sequences that can change in each generation , accounting for anticipation .
the discovery in rapid succession of several diseases caused by expansion of triplets raises the possibility that additional neuropsychiatrie disorders with clinical features of anticipation could be candidates .
the common properties of these mutations are the departures from mcndclian inheritance and the highly variable phenotype with wide - ranging age at onset , which are wellknown characteristics of schizophrenia .
more direct analyses of the genome have been made in order to detect large expansion of triplets in severe and early forms of schizophrenia , with conflicting and , above all , negative results .
the complexity of the methods required to detect a specific unstable mutation , and the clinical and genetic heterogeneity of schizophrenia , probably explain the presence of many negative studies and nonreplications of initially positive associations . on the other hand , epidemiological evidence in favor of anticipation
can be considered as very good , because it is based on many different samples and with numerous different methodological strategies .
nevertheless , the relationship between epidemiological anticipation and unstable genes remains to be proven in schizophrenia .
evidence for the anticipation effect is reinforced by the presence of a correlation for age at onset within sibships in our sample , with a younger age at onset in recent generations .
if the phc syndrome is considered as a moderate form of schizophrenia ( with moderate negative features and late age at onset ) , then it could be associated with a low number of triplet repeats ( but above the normal range ) .
the absence of affected ascendants and the 2.4% frequency of affected descendants are in accordance with this hypothesis .
the diagnosis of phc is mainly classified under schizophrenic disorders ( paranoid type ) according to dsm - iv , hampering the retrieval of these cases . according to dsm - iv , schizophrenia appears to be fundamentally heterogeneous and presumably consists of a group of related disorders . while cases of schizophrenia with onset after age 45 are mentioned , in the same way as early - onset cases , they are associated with a higher proportion of women , better occupational and marital histories , more paranoid delusions and hallucinations , and less disorganization and negative symptoms .
the clinical , epidemiological , and possibly etiopathogenic specificities of phc can not be helpful in delimiting the  schizophrenia spectrum  if phc is classified under the  schizophrenia  category , following the dsm - iv . in order to check the importance and specificities of phc , a subcategory for odd delusional disorders ( or even a specific category ) could be useful , not only for its clinical value , which was considered as obvious in france nearly a century ago , but also for the important problem of the phenotype boundaries in schizophrenia , for example , in genetic analyses .
the data provided herein may illustrate the fact that taking into consideration the phc phenotype could shed light on the clinical approach to the concept of anticipation in schizophrenia .
 the distinction between schizophrenia and chronic delusional syndromes ( including the french concept of  psychose hallucinatoire chronique  [ phc ] or chronic psychotic hallucinations , paraphrenia , and late paraphrenia ) is currently used in various european countries , although there are no international criteria for chronic and bizarre delusions . 
 the french concept of phc is characterized by late - onset psychosis , predominantly in females , with rich and frequent hallucinations , but almost no dissociative features or negative symptoms . 
 phc and late - onset schizophrenia may have risk factors in common , which may help differentiate these disorders from young - onset schizophrenia , especially with regard to the potential role of ( i ) the estradiol hypothesis ; ( ii ) the impact of sensory deficit ; ( hi ) putative specific brain abnormalities ; or ( iv ) specific genetic mutations . in accordance with this hypothesis , and taking into account the familial aggregation analyses of phc , here we evaluate the possibility that phc represents a less severe form of schizophrenia , which would partly explain the  sherman paradox  also observed in schizophrenia . 
 the sherman paradox describes the fact that multiplex families frequently have only one affected ascendant , meaning that an isolated sporadic case is at the origin of a highly loaded family . 
 we thus propose that if unstable mutations are involved in the risk for schizophrenia , then phc might represent a moderate disorder belonging to the schizophrenia spectrum phenotype . 
Clinical aspects
Risk factors
Brain imaging
Sensory deficit
Gender and hormonal status
Family history
Conclusion